Advances in characterisation, calibration and data processing speed of optical coherence tomography systems

This thesis describes advances in the characterisation, calibration and data processing of optical coherence tomography (OCT) systems. Femtosecond (fs) laser inscription was used for producing OCT-phantoms. Transparent materials are generally inert to infra-red radiations, but with fs lasers material modification occurs via non-linear processes when the highly focused light source interacts with the materials. This modification is confined to the focal volume and is highly reproducible. In order to select the best inscription parameters, combination of different inscription parameters were tested, using three fs laser systems, with different operating properties, on a variety of materials. This facilitated the understanding of the key characteristics of the produced structures with the aim of producing viable OCT-phantoms. Finally, OCT-phantoms were successfully designed and fabricated in fused silica. The use of these phantoms to characterise many properties (resolution, distortion, sensitivity decay, scan linearity) of an OCT system was demonstrated. Quantitative methods were developed to support the characterisation of an OCT system collecting images from phantoms and also to improve the quality of the OCT images. Characterisation methods include the measurement of the spatially variant resolution (point spread function (PSF) and modulation transfer function (MTF)), sensitivity and distortion. Processing of OCT data is a computer intensive process. Standard central processing unit (CPU) based processing might take several minutes to a few hours to process acquired data, thus data processing is a significant bottleneck. An alternative choice is to use expensive hardware-based processing such as field programmable gate arrays (FPGAs). However, recently graphics processing unit (GPU) based data processing methods have been developed to minimize this data processing and rendering time. These processing techniques include standard-processing methods which includes a set of algorithms to process the raw data (interference) obtained by the detector and generate A-scans. The work presented here describes accelerated data processing and post processing techniques for OCT systems. The GPU based processing developed, during the PhD, was later implemented into a custom built Fourier domain optical coherence tomography (FD-OCT) system. This system currently processes and renders data in real time. Processing throughput of this system is currently limited by the camera capture rate. OCTphantoms have been heavily used for the qualitative characterization and adjustment/ fine tuning of the operating conditions of OCT system. Currently, investigations are under way to characterize OCT systems using our phantoms. The work presented in this thesis demonstrate several novel techniques of fabricating OCT-phantoms and accelerating OCT data processing using GPUs. In the process of developing phantoms and quantitative methods, a thorough understanding and practical knowledge of OCT and fs laser processing systems was developed. This understanding leads to several novel pieces of research that are not only relevant to OCT but have broader importance. For example, extensive understanding of the properties of fs inscribed structures will be useful in other photonic application such as making of phase mask, wave guides and microfluidic channels. Acceleration of data processing with GPUs is also useful in other fields.

Stokes waves revisited:exact solutions in the asymptotic limit

The Stokes perturbative solution of the nonlinear (boundary value dependent) surface gravity wave problem is known to provide results of reasonable accuracy to engineers in estimating the phase speed and amplitudes of such nonlinear waves. The weakling in this structure though is the presence of aperiodic “secular variation” in the solution that does not agree with the known periodic propagation of surface waves. This has historically necessitated increasingly higher-ordered (perturbative) approximations in the representation of the velocity profile. The present article ameliorates this long-standing theoretical insufficiency by invoking a compact exact n-ordered solution in the asymptotic infinite depth limit, primarily based on a representation structured around the third-ordered perturbative solution, that leads to a seamless extension to higher-order (e.g., fifth-order) forms existing in the literature. The result from this study is expected to improve phenomenological engineering estimates, now that any desired higher-ordered expansion may be compacted within the same representation, but without any aperiodicity in the spectral pattern of the wave guides.

Quantitative determination of optical transmission through subwavelength slit arrays in Ag films: Role of surface wave interference and local coupling between adjacent slits

Measurement of the transmitted intensity from a coherent monomode light source through a series of subwavelength slit arrays in Ag films, with varying array pitch and number of slits, demonstrates enhancement (suppression) by factors of as much as 6 (9) when normalized to the transmission efficiency of an isolated slit. Pronounced minima in the transmitted intensity are observed at array pitches corresponding to lambda(SPP), 2 lambda(SPP), and 3 lambda(SPP), where lambda(SPP) is the wavelength of the surface plasmon polariton (SPP). The position of these minima arises from destructive interference between incident propagating waves and pi-phase-shifted SPP waves. Increasing the number of slits to four or more does not increase appreciably the per-slit transmission intensity. A simple interference model fits well the measured transmitted intensity profile.

Label-free detection of tobramycin in serum by transmission-localized surface plasmon resonance.

In order to improve the efficacy and safety of treatments, drug dosage needs to be adjusted to the actual needs of each patient in a truly personalized medicine approach. Key for widespread dosage adjustment is the availability of point-of-care devices able to measure plasma drug concentration in a simple, automated, and cost-effective fashion. In the present work, we introduce and test a portable, palm-sized transmission-localized surface plasmon resonance (T-LSPR) setup, comprised of off-the-shelf components and coupled with DNA-based aptamers specific to the antibiotic tobramycin (467 Da). The core of the T-LSPR setup are aptamer-functionalized gold nanoislands (NIs) deposited on a glass slide covered with fluorine-doped tin oxide (FTO), which acts as a biosensor. The gold NIs exhibit localized plasmon resonance in the visible range matching the sensitivity of the complementary metal oxide semiconductor (CMOS) image sensor employed as a light detector. The combination of gold NIs on the FTO substrate, causing NIs size and pattern irregularity, might reduce the overall sensitivity but confers extremely high stability in high-ionic solutions, allowing it to withstand numerous regeneration cycles without sensing losses. With this rather simple T-LSPR setup, we show real-time label-free detection of tobramycin in buffer, measuring concentrations down to 0.5 μM. We determined an affinity constant of the aptamer-tobramycin pair consistent with the value obtained using a commercial propagating-wave based SPR. Moreover, our label-free system can detect tobramycin in filtered undiluted blood serum, measuring concentrations down to 10 μM with a theoretical detection limit of 3.4 μM. While the association signal of tobramycin onto the aptamer is masked by the serum injection, the quantification of the captured tobramycin is possible during the dissociation phase and leads to a linear calibration curve for the concentrations over the tested range (10-80 μM). The plasmon shift following surface binding is calculated in terms of both plasmon peak location and hue, with the latter allowing faster data elaboration and real-time display of the results. The presented T-LSPR system shows for the first time label-free direct detection and quantification of a small molecule in the complex matrix of filtered undiluted blood serum. Its uncomplicated construction and compact size, together with the remarkable performances, represent a leap forward toward effective point-of-care devices for therapeutic drug concentration monitoring.

Wave trapping in a two-dimensional sound-soft or sound-hard acoustic waveguide of slowly-varying width

In this paper we derive novel approximations to trapped waves in a two-dimensional acoustic waveguide whose walls vary slowly along the guide, and at which either Dirichlet (sound-soft) or Neumann (sound-hard) conditions are imposed. The guide contains a single smoothly bulging region of arbitrary amplitude, but is otherwise straight, and the modes are trapped within this localised increase in width. Using a similar approach to that in Rienstra (2003), a WKBJ-type expansion yields an approximate expression for the modes which can be present, which display either propagating or evanescent behaviour; matched asymptotic expansions are then used to derive connection formulae which bridge the gap across the cut-off between propagating and evanescent solutions in a tapering waveguide. A uniform expansion is then determined, and it is shown that appropriate zeros of this expansion correspond to trapped mode wavenumbers; the trapped modes themselves are then approximated by the uniform expansion. Numerical results determined via a standard iterative method are then compared to results of the full linear problem calculated using a spectral method, and the two are shown to be in excellent agreement, even when $\epsilon$, the parameter characterising the slow variations of the guide’s walls, is relatively large.

Bulk plasmon polariton-gap soliton-induced transparency in one-dimensional Kerr-metamaterial superlattices

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The optical response of nanostructured surfaces and the composite diffracted evanescent wave model

Investigations of the optical response of subwavelength-structure arrays milled into thin metal films have revealed surprising phenomena, including reports of unexpectedly high transmission of light. Many studies have interpreted the optical coupling to the surface in terms of the resonant excitation of surface plasmon polaritons (SPPs), but other approaches involving composite diffraction of surface evanescent waves (CDEW) have also been proposed. Here we present a series of measurements on very simple one-dimensional subwavelength structures to test the key properties of the surface waves, and compare them to the CDEW and SPP models. We find that the optical response of the silver metal surface proceeds in two steps: a diffractive perturbation in the immediate vicinity (2–3 mu m) of the structure, followed by excitation of a persistent surface wave that propagates over tens of micrometres. The measured wavelength and phase of this persistent wave are significantly shifted from those expected for resonance excitation of a conventional SPP on a pure silver surface.

Conception, fabrication et caractérisation d'un biocapteur SPR à base de guides d'ondes photoniques sur substrat de verre

Résumé : Malgré le nombre croissant de capteurs dans les domaines de la chimie et la biologie, il reste encore à étudier en profondeur la complexité des interactions entre les différentes molécules présentes lors d’une détection à l’interface solide-liquide. Dans ce cadre, il est de tout intérêt de croiser différentes méthodes de détection afin d’obtenir des informations complémentaires. Le principal objectif de cette étude est de dimensionner, fabriquer et caractériser un détecteur optique intégré sur verre basé sur la résonance plasmonique de surface, destiné à terme à être combiné avec d’autres techniques de détection, dont un microcalorimètre. La résonance plasmonique de surface est une technique reconnue pour sa sensibilité adaptée à la détection de surface, qui a l’avantage d’être sans marquage et permet de fournir un suivi en temps réel de la cinétique d’une réaction. L’avantage principal de ce capteur est qu’il a été dimensionné pour une large gamme d’indice de réfraction de l’analyte, allant de 1,33 à 1,48. Ces valeurs correspondent à la plupart des entités biologiques associées à leurs couches d’accroche dont les matrices de polymères, présentés dans ce travail. Étant donné que beaucoup d’études biologiques nécessitent la comparaison de la mesure à une référence ou à une autre mesure, le second objectif du projet est d’étudier le potentiel du système SPR intégré sur verre pour la détection multi-analyte. Les trois premiers chapitres se concentrent sur l’objectif principal du projet. Le dimensionnement du dispositif est ainsi présenté, basé sur deux modélisations différentes, associées à plusieurs outils de calcul analytique et numérique. La première modélisation, basée sur l’approximation des interactions faibles, permet d’obtenir la plupart des informations nécessaires au dimensionnement du dispositif. La seconde modélisation, sans approximation, permet de valider le premier modèle approché et de compléter et affiner le dimensionnement. Le procédé de fabrication de la puce optique sur verre est ensuite décrit, ainsi que les instruments et protocoles de caractérisation. Un dispositif est obtenu présentant des sensibilités volumiques entre 1000 nm/RIU et 6000 nm/RIU suivant l’indice de réfraction de l’analyte. L’intégration 3D du guide grâce à son enterrage sélectif dans le verre confère au dispositif une grande compacité, le rendant adapté à la cointégration avec un microcalorimètre en particulier. Le dernier chapitre de la thèse présente l’étude de plusieurs techniques de multiplexage spectral adaptées à un système SPR intégré, exploitant en particulier la technologie sur verre. L’objectif est de fournir au moins deux détections simultanées. Dans ce cadre, plusieurs solutions sont proposées et les dispositifs associés sont dimensionnés, fabriqués et testés.

T-wave alternans: desempenho clínico, limitações, metodologias de análise

Reconhecer com precisão indivíduos com maior risco imediato de morte súbita cardíaca (MSC) ainda é uma questão em aberto. A natureza fortuita dos eventos cardiovasculares agudos não parece se adequar ao conhecido modelo de indução de taquicardia/fibrilação ventricular por um gatilho em sincronia a um substrato arritmogênico estático. Quanto ao mecanismo da MSC, uma instabilidade elétrica dinâmica explicaria melhor a raridade da associação simultânea de um gatilho certo a um substrato cardíaco apropriado. Diversos estudos tentaram medir essa instabilidade elétrica cardíaca (ou um equivalente válido) em uma sequência de batimentos cardíacos no ECG. Dentre os mecanismos possíveis podemos citar o prolongamento do QT, dispersão do QT, potenciais tardios, alternância de onda T ou T-wave alternans (TWA), e turbulência da frequência cardíaca. Este artigo se atém em particular ao papel da TWA no panorama atual da estratificação de risco cardíaco. Os achados sobre TWA ainda são heterogêneos, variando de um desempenho prognóstico muito bom até um quase nulo, dependendo da população clínica observada e protocolo clínico usado. Para preencher as atuais lacunas no conhecimento sobre TWA, profissionais médicos e pesquisadores devem explorar melhor as características técnicas das diversas tecnologias disponíveis para a avaliação de TWA e atentar ao fato de que os valores de TWA respondem a diversos outros fatores, além de medicamentos. Informações sobre mecanismos celulares e subcelulares da TWA estão fora do escopo deste artigo, mas são referenciados alguns dos principais trabalhos sobre este tópico, com o intuito de auxiliar no entendimento dos conceitos e fatos cobertos neste artigo.

Determination of 5-aminosalicylic acid in pharmaceutical formulations by square wave voltammetry at pencil graphite electrodes

An analytical method for the determination of the anti-inflammatory drug 5-aminosalicylic acid (5-ASA) in pharmaceutical formulations using square wave voltammetry at pencil graphite electrodes was developed. After the optimization of the experimental conditions, calibration curves were obtained in the linear concentration range from 9.78 × 10-7 to 7.25 × 10-5 mol L-1 resulting in a limit of detection of 2.12 ± 0.05 x 10-8 mol L-1. Statistical tests showed that the concentrations of 5-ASA in commercial tablets and enemas obtained with the proposed voltammetric method agreed with HPLC values at a 95% confidence level.

Brazilian offshore wave climate based on NWW3 reanalysis

This paper provides a description of the wave climate off the Brazilian coast based on an eleven-year time series (Jan/1997-Dec/2007) obtained from the NWW3 operational model hindcast reanalysis. Information about wave climate in Brazilian waters is very scarce and mainly based on occasional short-term observations, the present analysis being the first covering such temporal and spatial scales. To define the wave climate, six sectors were defined and analyzed along the Brazilian shelf-break: South (W1), Southeast (W2), Central (W3), East (W4), Northeast (W5) and North (W6). W1, W2 and W3 wave regimes are determined by the South Atlantic High (SAH) and the passage of synoptic cold fronts; W4, W5 and W6 are controlled by the Intertropical Convergence Zone (ITCZ) and its meridional oscillation. The most energetic waves are from the S, generated by the strong winds associated to the passage of cold fronts, which mainly affect the southern region. Wave power presents a decrease in energy levels from south to north, with its annual variation showing that the winter months are the most energetic in W1 to W4, while in W5 and W6 the most energetic conditions occur during the austral summer. The information presented here provides boundary conditions for studies related to coastal processes, fundamental for a better understanding of the Brazilian coastal zone.

Evaluation of left ventricular diastolic echocardiographic parameters in healthy dogs by pulsed-wave Doppler

Left ventricular diastolic dysfunction plays an important role on heart failure progression. In order to obtain additional reference values of left ventricular diastolic parameters and investigate influence of common variables, peak E wave (peak E), peak A wave (peak A), E/A ratio (E/A), E wave deceleration time (EDT) and isovolumic relaxation time (IRVT) were studied in 40 clinically healthy dogs, by pulsed wave Doppler. The following values were obtained: peak E = 0.747 ± 0.117 m/s, peak A = 0.487 ± 0.062 m/s, E/A = 1.533 ± 0.198, EDT = 88.7 ± 9.2 ms and IRVT = 0.080 ± 0.009 s. Some parameters were influenced by heart rate (peak E, peak A and IRVT), by age (peak A and E/A) and by body weight (TRIV). Gender influence was absent. Values obtained can be used as reference for canine specimens but its interpretation should consider on the influence of related variables.

Surface-plasmon-enhanced frequency upconversion in Pr(3+) doped tellurium-oxide glasses containing silver nanoparticles

A frequency upconversion process in Pr(3+) doped TeO(2)-ZnO glasses containing silver nanoparticles is studied under excitation with a nanosecond laser operating at 590 nm, in resonance with the (3)H(4)-->(1)D(2) transition. The excited Pr(3+) ions exchange energy in the presence of the nanoparticles, originating efficient conversion from orange to blue. The enhancement in the intensity of the luminescence at similar to 482 nm, corresponding to the (3)P(0)-->(3)H(4) transition, is due to the influence of the large local field on the Pr(3+) ions, which are located near the metallic nanoparticles. (C) 2008 American Institute of Physics.

Surface plasmon resonance of gold nanoparticles formed by cathodic arc plasma ion implantation into polymer

Shallow subsurface layers of gold nanoclusters were formed in polymethylmethacrylate (PMMA) polymer by very low energy (49 eV) gold ion implantation. The ion implantation process was modeled by computer simulation and accurately predicted the layer depth and width. Transmission electron microscopy (TEM) was used to image the buried layer and individual nanoclusters; the layer width was similar to 6-8 nm and the cluster diameter was similar to 5-6 nm. Surface plasmon resonance (SPR) absorption effects were observed by UV-visible spectroscopy. The TEM and SPR results were related to prior measurements of electrical conductivity of Au-doped PMMA, and excellent consistency was found with a model of electrical conductivity in which either at low implantation dose the individual nanoclusters are separated and do not physically touch each other, or at higher implantation dose the nanoclusters touch each other to form a random resistor network (percolation model). (C) 2009 American Vacuum Society. [DOI: 10.1116/1.3231449]