This Ph.D. thesis addresses remote sensing of the atmosphere by means of lidar and S-band clear-air weather radar, and related data signal processing. Active remote sensing by means of these instruments offers unprecedented capabilities of spatial and temporal resolutions for vertical atmospheric profiling and the retrieval of key optical and physical atmospheric products in an increasing environmental regulatory framework. The first goal is this Ph.D. concerns the estimation of error bounds in the inversion of the profile of the atmospheric backscatter coefficient from elastic lidar signals (i.e., without wavelength shift in reception when interacting with atmospheric scatterers) by means of the two-component inversion algorithm (the so-called Klett-Fernald-Sasano¿s algorithm). This objective departs from previous works at the Remote Sensing Lab. (RSLab) of the Universitat Politècnica de Catalunya (UPC) and derives first-order error-propagated bounds (approximate) and total-increment bounds (exact). As distinctive feature in the state of the art, the error bounds merge into a single body both systematic (i.e., user-calibration inputs) and random error sources (finite signal-to-noise ratio, SNR) yielding an explicit mathematical form. The second goal, central to this Ph.D., tackles retrieval of the Atmospheric Boundary Layer Height (ABLH) from elastic lidar and S-band Frequency-Modulated Continuous-Wave (FMCW) radar observations by using adaptive techniques based on the Extended Kalman Filter (EKF). The filter is based on morphological modelling of the Mixing-Layer-to-Free-Troposphere transition and continuous estimation of the noise covariance information. In the lidar-EKF realization the proposed technique is shown to outperform classic ABLH estimators such as those based on derivative techniques, thresholded decision, or the variance centroid method. The EKF formulation is applied to both ceilometer and UPC lidar records in high- and low-SNR scenes. The lidar-EKF approach is re-formulated and successfully extended to S-band radar scenes (Bragg¿s scattering) in presence of interferent noise sources (Rayleigh scattering from e.g., insects and birds). In this context, the FMCW feature enables the range-resolved capability. EKF-lidar and EKF-radar ABLH estimates are cross-examined from field campaign results. Finally, the third goal deals with exploitation of the existing UPC lidar station: In a first introductory part, a modified algorithm for enhancing the dynamic range of elastic lidar channels by ¿gluing¿ analog and photon-counting data records is formulated. In a second part, two case examples (including application of the gluing algorithm) are presented to illustrate the capabilities of the UPC lidar in networked atmospheric observation of two recent volcano eruption events as part of the EARLINET (European Aerosol Research Lidar Network). The latter is part of GALION (Global Atmospheric Watch Atmospheric Lidar Observation Network)-GEOSS (Global Earth Observation System of Systems) framework. / La tesis doctoral aborda la teledetecció atmosfèrica amb tècniques lidar i radar (banda S) i llur tractament del senyal. La teledetecció activa amb aquests instruments ofereix resolucions espacials i temporals sense precedents en la perfilometria vertical de l'atmosfera i recuperació de productes de dades òptics i físics atmosfèrics en un marc de creixent regulació mediambiental. El primer objectiu d'aquesta tesi concerneix l'estimació de cotes d'error en la inversió del perfil del coeficient de retrodispersió atmosfèrica a partir de senyals lidar de tipus elàstic (és a dir, sense desplaçament de la longitud d'ona en recepció al interactuar amb els dispersors atmosfèrics) mitjançant l'algorisme d'inversió de dues components de Klett-Fernald-Sasano. Aquest objectiu parteix de treballs previs en el Remote Sensing Lab. (RSLab) de la Universitat Politècnica de Catalunya (UPC) i permet obtenir cotes de primer ordre (aproximades) basades en propagació d'errors i cotes (exactes) basades en el increment total de l'error. Característica diferencial en front l'estat de l'art és l'assimilació d'errors sistemàtics (per exemple, entrades de cal.libració d'usuari) i aleatoris (relació senyal-soroll, SNR, finita) en forma matemàtica explícita. El segon objectiu, central de la tesis, aborda l'estimació de l'altura de la capa límit atmosfèrica (ABLH) a partir de senyal lidar elàstics i d'observacions radar en banda S (ona continua amb modulació en freqüència, FMCW) utilitzant tècniques adaptatives basades en filtrat estès de Kalman (EKF). El filtre es basa en modelat morfològic de la transició atmosfèrica entre la capa de mescla i la troposfera lliure i en l'estimació continua de la informació de covariança del soroll. En el prototipus lidar-EKF la tècnica proposada millora clarament les tècniques clàssiques d'estimació de la ABLH como són les basades en mètodes derivatius, decisió de llindar, o el mètode de la variança-centroide. La formulació EKF s'aplica tant a mesures procedents de ceilòmetres lidar como de la pròpia estació lidar UPC en escenes d'alta i baixa SNR. Addicionalment, l'enfoc lidar-EKF es reformula i s'estén amb èxit a escenes radar en banda S (dispersió Bragg) en presència de fonts de soroll interferent (dispersió Rayleigh de, per exemple, insectes i ocells). En aquest context, la característica FMCW permet la capacitat de resolució en distància. L'estimació de la ABLH amb els prototipus lidar-EKF i radar-EKF s'intercompara en campanyes de mesura. Finalment, el tercer objectiu atén a l'explotació de l'estació lidar UPC existent: En una primera part introductòria, es formula un algorisme modificat de "gluing" per a la millora del marge dinàmic de canals lidar elàstics mitjançant combinació (o "enganxat") de senyals lidar adquirits analògicament i amb foto-comptatge. En una segona part, es presenten dos exemples (incloent l'aplicació de l'algorisme de "gluing") que il.lustren les capacitats del lidar de la UPC en l'observació atmosfèrica de dos recents erupcions volcàniques des de la xarxa d'observació EARLINET (European Aerosol Research Lidar Network). Aquesta última és part de GALION (Global Atmospheric Watch Atmospheric Lidar Observation Network)-GEOSS (Global Earth Observation System of Systems).

Historical decorated glass and glazed ceramics are studied with the object to determine the technology of production and to relate it with the optical properties (colour, shine, opacity). Four different case of study are investigated: production technology and replication of lead antimonate yellow glass from New Kingdom Egypt and the Roman Empire, technology of production of polychrome lustre, analyses of Syrian lustre pottery (12th–14th centuries AD) and study of color and dichroism of silver stained glasses. These different coloured glazes or glasses have in common to be produced by the presence of micro or nanoparticles embedded into the glaze which give their special optical effect. Chemical and microstructural analyses are performed using a selection of complementary Microscopic and Spectroscopic techniques that are the most adequate for the analyses of each decoration. Physical optical properties are also modeled and measured by means of UV-Vis spectroscopy. The composition and structure of the different phases formed during the processing of the decorations in historical times is obtained with the object to learn about their stability and processing conditions and to relate them to their optical properties

"La imatge neutra: la fotografia com a model en la pintura de finals del segle XX " estudia la influència que ha tingut el mitjà fotogràfic, tant en el procés analògic com en digital, en la transformació dels paràmetres establerts per la modernitat de la pintura de finals del segle XX, a partir d'anàlisis dels corrents i artistes més significatius del debat, vinculats tots ells amb l'obra artística de l'autor.Es demostra com la imatge òptica canvia la nostra manera de percebre la realitat, i com això ha estat motiu i forma de molts dels corrents figuratius, que han aparegut en la pintura a partir dels anys seixanta. Tracta de veure com la fotografia, lluny d'obstaculitzar el procés natural de la pintura, ha contribuït a donar-li noves perspectives formals i conceptuals. Estudia la funció codificadora que exerceixen els models fotogràfics en el producte artístic final, i mostra com la pintura accepta els seus límits i deixa contaminar-se per altres disciplines, en detriment de la puresa formal, per situar-se en un lloc més modest, però que continua sent efectiu. / "The neutral image: photography as a model in late twentieth century painting" studies the influence of photography, both analog and digital, in the transformation of the painting of the end of the twentieth century. It does so via an analysis of the most significant trends and artists in the debate, all of them linked to the artistic work of the author.The study shows how optical images change the ways in which we perceive reality, and how they have both inspired and shaped many of the figurative trends that have appeared in painting since the nineteen sixties. It reflects on how photography, far from hindering the natural process of painting, has contributed to providing it with new formal and conceptual perspectives. It studies the encoding function of photographic models in the final artistic product, and shows how painting accepts its limits and is open to influence by other disciplines, to the detriment of formal purity, to find its new position - a more modest position, but one that nonetheless remains effective.

Dentro de la denominación --reconocimiento de formas' se engloban todos aquellos métodos mediante los cuales es posible detectar la presencia de una determinada imagen (referencia) dentro de otra (escena). Del conjunto de técnicas ópticas que permiten realizar esta operación, destacan las basadas en la comparación entre los diferentes elementos que forman la escena y la imagen que se quiere detectar. Este método comparativo, denominado correlación óptica, aprovecha las propiedades de las lentes y su capacidad para realizar transformadas de Fourier. Los dispositivos utilizados para realizar la correlación óptica reciben el nombre genérico de correladores. La investigación realizada tiene como objetivo principal el estudio de los efectos que las aberraciones de los sistemas ópticos presentes en los correladores provocan en el proceso de reconocimiento. Para realizar este análisis se ha desarrollado un método de cálculo de la aberración de onda de un sistema óptico con simetría de revolución y un objeto puntual situado sobre el eje óptico. Este método utiliza el trazado exacto de rayos y las relaciones existentes entre la aberración de rayo y la aberración de onda. Se basa también en la teoría de formación de imagen de Abbe-Rayleigh, la cuál agrupa todos los efectos difractivos en las pupilas del sistema, bien en la de entrada o en la de salida, y utiliza la óptica geométrica para describir la propagación de la luz entre ambas. La fiabilidad del método se ha contrastado experimentalmente mediante técnicas interferómetricas, y se han comparado los resultados para la aberración de onda con los calculados por programas comerciales de diseño y evaluación de sistemas ópticos. Una vez garantizado el correcto funcionamiento de los algoritmos de cálculo, se han analizado dos arquitecturas clásicas de correlación: el correlador de transformadas conjuntas monobanco y el correlador convergente de Vander Lugt. En el primero de ellos se ha realizado un estudio independiente de la influencia de la aberración de cada uno de los difractómetros que lo forman en la correlación final, y a partir de los resultados obtenidos se propone un método de optimización del correlador. Este estudio también se ha realizado para el correlador de Vander Lugt, con resultados similares. En el caso de este segundo correlador también se ha estudiado la inclusión de la información sobre la aberración de ambas etapas del correlador en el diseño de los filtros. Finalmente, basándose en los resultados obtenidos, se propone una nueva configuración que mejora de forma sustancial el comportamiento del mismo como equipo de reconocimiento de formas, llegando a anular completamente la influencia de la aberración. / The aim of this work is to study the influence of the aberrations in optical correlators, and how they affect the correlation peak heights.In order to perform it, a numerical method has been developed. This method calculates the wave aberration of a symmetrical optical system with a point source located at the optical axis. The evaluation of the wave aberration is carried out by means of an exact ray-tracing algorithm which computes the aberration at the different points of the exit pupil according to the relations between wave aberration and ray aberration. Lenses and other stops in the system are assumed to be large enough not to significantly cut the wave front so that light propagation can be accurately described by geometrical optics from the light source to the exit pupil (Abbe-Rayleigh theory of image formation). The method has been experimentally validated by means of interferometric techniques, and the results for the wave aberration have been compared to those calculated by a standard optical design software. Once the right behavior of the algorithm has been guaranteed, two main correlation architectures have been analized: the converging joint transform correlator (JTC) and the converging Vander Lugt correlator (VdLC). In JTC, three different situations have been explored: we consider the aberration only in the first diffraction stage (generation of power spectrum), then only in the second (transformation of power spectrum into correlation) and finally, in both steps simultaneously. Using the results obtained in this study, a simple optimization method is introduced. This method allows the best working conditions for an optical system to be derived.These three situations have been also analyzed in VdLC, and a similar influence from each stage has been found. The correlation process in this architecture uses complex filters, which are usually generated from the image to be detected, free from aberrations. In this part, filters have been designed including information about the aberrations of the optical systems. Finally, a new arrangement which improves the correlation process and cancels the influence of the aberration is proposed.

En aquest treball s'ha desenvolupat un protocol de classificació supervisada (també anomenat reconeixement de patrons: Pattern Recognition) d'imatges segmentades basat en l'extracció de característiques invariants a les transformacions geomètriques no deformatives i la utilització de mètodes multi variants de classificació, optimitzant el temps de càlcul. Per tant, com que les característiques calculades són invariants, s'ha aconseguit classificar les imatges independentment de la mida d'aquestes i posició i l'orientació d'aquestes dintre de l'escena. També s'ha aconseguit una taxa d'encerts de classificació propera al 100 % en els casos pràctics duta a terme.

The purpose of this PhD thesis was to design, implement and validate a low cost compact system based on the double-pass I technique in order to evaluate the viability of its use in the future in optical instrumentation to obtain optical quality and light diffusior estimations. First of all we measured the optical quality of an electro-optical liquid lens to prove its usefulness in the measurement of the eye's optical quality. We built a simple single-pass setup composed by a laser diode (LD), an electro-opticalliquid lens (EOLL) and a CCD as recording device. The results obtained in this study show the validity of this type of lenses for corrections of spherical refractive errors. In second place we studied the correction of spherical refractive errors in double-pass configurations by means of the electro­ optical liquid lens (EOLL). We measured the optical performance of the spherical corrector in terms of optical power, pupil size and optical quality verifying that they all fit the requirements to be applied to double-pass systems. We also evaluated the performance of the proposed method in patients by comparison with a conventional double-pass system using a Badal optometer (OQAS instrument) and we conclude that the EOLL is suitable to be used in a double-pass system for a spherical correction. In third place we implemented and validated a superluminiscent led (SLED) as light source in the double-pass system . The study showed that the SLED used during the experimentation did not have sufficiently low coherence to break the speckle noise on its own, but showed a good performance when being combined with other methods for speckle reduction. In fourth place we implemented and validated a CMOS camera as recorder device in the double-pass system. We studied the performance of a CMOS camera by comparison with the results obtained with a CCD. The study showed a high correlation between the results obtained with the CCD and CMOS camera, demonstrating in this manner suitability of this type of sensors (CMOS) for application in the field of visual optics. Taking into account the results on the light source, the spherical refractive error corrector, and the recording device, the final configuration of the system includes a SLD light source, a corrector based on EOLLs and a CMOS camera. The experimental double-pass system has been compared with a commercially available double-pass system (OQAS). All the tests showed the good agreement between both systems, which suggest that the system here presented may be used for estimations of the ocular optical quality and scattering measurements. We conclude that the proposed experimental setup, including as innovations the CMOS camera and the EOLL spherical corrector, improves in terms of size and cost a conventional system with a performance comparable to that observes in commercially available devices. / Esta tesis doctoral ha tenido como objetivo fundamental el diseño, implementación y validación de un sistema compacto y de bajo coste basado en la técnica del doble paso que nos permita obtener estimaciones de calidad óptica en general y de luz difusa en particular, dirigido a una posible futura utilización en la práctica clínica. Para ello se ha partido del esquema de doble paso utilizado en el instrumento oftalmológico OQAS y se ha estudiado y validado posibles mejoras, tanto en grado de integración como en coste, que han garantizado las mismas o superiores prestaciones. En primer lugar se procedió a la validación de una lente electro-óptica como sistema de corrección de la refracción esférica, este dispositivo sustituye al tradicional sistema Badal compuesto por dos lentes cuya distancia relativa puede variarse, lo cual permite la corrección de la refracción esférica. Se analizó y demostró la validez de este nuevo tipo de lentes electro-ópticas para la corrección de refracción esférica. En segundo lugar se procedió al diseño y la implementación de un sistema de doble paso utilizando la lente electro-óptica para la compensaci6n de refracción esférica. Una vez se comprobó que la lente electro-óptica reunía los requisitos de calidad óptica, se procedió a implementar el sistema de doble paso que incorpora dicha lente en substitución del sistema Badal. Se verificó y demostró que el sistema con la lente electro-óptica tiene prestaciones similares o mejores que el clásico sistema de doble paso. En tercer lugar se implementó y validó el sistema de iluminación basado en una fuente LED superluminiscente (SLED). Se incorporó como fuente de luz al sistema de doble paso un SLED y se analizó el grado de ruido speckle en las imágenes obtenidas. El estudio determinó que el SLED utilizado no tenía la suficiente baja coherencia como para romper el ruido speckle por sí mismo, pero si mostró un buen rendimiento cuando se combina con otros métodos para la reducción del speckle. En cuarto lugar se procedió a implementar y validar el sistema de registro basado en una tecnología CMOS. Se incorporó una cámara CMOS como nuevo dispositivo de registro al sistema de doble paso. El estudio realizado puso de manifiesto una alta correlación existente entre los resultados obtenidos con la cámara CMOS y la CCD, de manera que quedó demostrado la idoneidad de este tipo de sensores (CMOS) para la aplicación en montajes experimentales de óptica visual y para la implementación de instrumentación asociada a este campo. Ya por último se procedió a la validación del sistema de doble paso resultante. En función de los resultados obtenidos se implementó el sistema de doble paso definitivo siguiendo criterios de simplicidad y coste, este sistema incorpora un compensador de refracción esférica basado en una lente electro-óptica, un diodo laser y una cámara CMOS. Para la validación de los resultados obtenidos y como equipo comercial de referencia se utilizó el instrumento clínico OQAS. Los resultados obtenidos en el estudio demostraron una alta correlación entre el sistema experimental y el instrumento OQAS. Así pues y a la vista de los resultados obtenidos se concluye que a partir de los diferentes estudios realizados en esta tesis doctoral se ha demostrado que el sistema de doble paso presentado basado en una lente electro-óptica, un diodo laser y una cámara CMOS mejora en cuanto a dimensiones y coste el de un sistema convencional.

A interferometria holográfica é um poderoso método óptico para observação de fenômenos perturbativos e na análise de superfícies, sendo extremamente útil em aplicações em pesquisa básica, biomédicas e tecnológicas. Os cristais fotorefrativos se apresentam como um meio atrativo para registro de hologramas. O fenômeno que caracteriza esses cristais é o efeito fotorrefrativo. Tal efeito consiste na modulação do índice de refração através de fotoindução e efeito eletro-óptico linear (Efeito Pockels), o que permite o registro de hologramas de fase em volume. Entre as características que recomendam os cristais fotorrefrativos para interferometria holográfica podemos citar: o processo de registro e leitura ocorre de maneira dinâmica através da técnica de mistura de duas ondas; o fato de serem meios revers´?veis dispensando processamento químico e a boa resolução implicando imagens holográficas de boa qualidade. Analisamos as diversas tensões que ocorrem no processo mastigatório, estudando principalmente a concentração de cargas e as dissipações nesse processo, utilizando a técnica holográfica de dupla exposição e o cristal fotorrefrativo Bi12SiO20 (BSO), da família das Silenitas, como meio de registro. O estudo em crânio seco e a simulação dos principais feixes dos músculos da mastigação permitem realizar a contração dos mesmos, com aproximação melhor que os métodos de elementos finitos e resinas fotoelásticas, em estruturas anisotrópicas como o crânio. / The holographic interferometry is a powerful optical method for observation of the disturbance phenomena and in the analysis of surface, being extremely useful in application in basic research, biomedical and technological. The photorefractive crystals present as an attractive holographic recording medium. The phenomenon that characterize these crystals is the photorefractive effect. Such effect consistis of the index of refraction modulation grating via the linear eletro-optic effect (the Pockels effect) and photoindution, that it allow phase holographic recording in volume. Among the characteristics that admit the photorefractive crystals for holographic interferometry we can cite: recording and reading tecniques to occur in dynamics way through the tecnique of two-wave mixing, it is reversible medium resulting holographic images of good quality. We analyze the varied strains that occur in the masticatory process, mainly studying the load concentration and the dissipation in this process, using the double-exposure holographic technique and the photorefractive crystals Bi12SiO20 (BSO), of the sillenite family, as holographic recording medium. The study in dry skull and the simulation of main beams of the mastication muscles allow to realize the concentration of the same ones, with better approach than the methods of finite elements and photoelastics resins, in anisotropic structures as the skull.

The increasing need for range-resolved aerosol and water-vapour atmospheric observation networks worldwide has given rise to multi-spectral LIDARs (Light Detection and Ranging, a synonym of laser radar) as advanced remote sensing sensors. This Ph.D. presents the design, integration and analysis of the new 6-channel multispectral elastic/Raman LIDAR for aerosol and water-vapour content monitoring developed at the Remote Sensing Lab. (RSLAB) of the Universitat Polit ecnica de Catalunya (UPC). It is well known that the combination of at least three elastic and two Raman nitrogen channels are su cient to enable retrieval of the optical and microphysical properties of aerosols with a key impact on climate change variables. The UPC lidar is part of the EARLINET (European Aerosol Research Lidar Network) -GALION (Global Atmospheric Watch Atmospheric Lidar Observation Network), a ground-based continental network including more than 28 stations. Currently, only 8 of the 28 EARLINET stations are of such advanced type. This Ph.D. speci cally focuses on: (1) Concept link-budget instrument design and overlap factor assessment. The former includes opto-atmospheric parameter modelling and assessment of backscattered power and SNR levels, and maximum system range for the di erent reception channels (3 elastic, and 2 aerosol and 1 water-vapour Raman channels, ultraviolet to near-infrared bands). The latter studies the laser-telescope crossover function (or overlap function) by means of a novel raytracing Gaussian model. The problem of overlap function computation and its near-range sensitivity for medium size aperture (f=10, f=11) bi-axial tropospheric lidar systems using both detector and ber-optics coupling alternatives at the telescope focal-plane is analysed using this new ray-tracing approach, which provides a much simpler solution than analyticalbased methods. Sensitivity to laser divergence, eld-lens and detector/ ber positions, and ber's numerical aperture is considered. (2) Design and opto-mechanical implementation of the 6-channel polychromator (i.e., the spectrally selective unit in reception). Design trade-o s concerning light collimation, end-to-end transmissivity, net channel responsivity, and homogeneous spatial light distribution onto the detectors' active area discussed. (3) System integration and validation. This third part is two fold: On one hand, fi rst-order backscatter-coe cient error bounds (a level-1 data product) for the two-component elastic lidar inversion algorithm are estimated for both random (observation noise) and systematic error sources (user's uncertainty in the backscatter-coe cient calibration, and user's uncertainty in the aerosol extinction-to-backscatter lidar ratio). On the other hand, the multispectral lidar so far integrated is described at both hardware and control software level. Statistical validation results for the new UPC lidar (today in routine operation) in the framework of SPALI-2010 intercomparison campaign are presented as part of EARLINET quality assurance / optimisation of instruments' program. The methodology developed in the rst part of this Ph.D. has successfully been applied to the speci cation case study of the IFAE/UAB lidar system, which will be installed and operated at the Cherenkov Telescope Array (CTA) observatory. Finally, specs for automated unmanned unattended lidar operation with service times close to 365/24 are presented at the end of this Ph.D. in response to the increasing demand for larger observation times and availability periods of lidar stations.

Noninvasive measurement of hemodynamics at the microvascular level may have a great impact on oncology in clinics for diagnosis, therapy planning and monitoring, and, in preclinical studies. To this end, diffuse optics is a strong candidate for noninvasive, repeated, deep tissue monitoring. In this multi-disciplinary, translational work, I have constructed and deployed hybrid devices which are the combination of two qualitatively different methods, near infrared diffuse optical spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS), for simultaneous measurement of microvascular total hemoglobin concentration, blood oxygen saturation and blood flow. In a preclinical study, I applied the hybrid device to monitor the response of renal cell carcinoma in mice to antiangiogenic therapy. The results suggest that we can predict the output of therapy from early hemodynamic changes, which provide us with valuable information for better understanding of the tumor resistance mechanism to antiangiogenic therapies. In two in vivo studies in human volunteers, I have developed protocols and probes to demonstrate the feasibility of noninvasive diffuse optical spectroscopy to investigate the pathophysiology of bone. First study was study on the physiology of the patella microvasculature, the other introduced the manubrium as a site that is rich in red bone mar- row and accessible to diffuse optics as a potential window to monitor the progression of hematological malignancies. Overall, during my Ph.D., I have developed instrumentation, algorithms and protocols and, then, applied this technique for preclinical and clinical investigations. My research is a link between preclinical and clinical studies and it opens new areas of applications in oncology. / La medición no invasiva de la hemodinámica a nivel microvascular puede alcanzar un gran impacto en oncología: en las clínicas para el diagnóstico, la planeación y monitorización de las terapias, y en estudios preclínicos. La óptica difusa es una fuerte candidata para la monitorización no invasiva y repetida del tejido profundo. En este trabajo multidisciplinario y traslacional, construí e implementé dispositivos híbridos que son la combinación de dos métodos cualitativamente diferentes: espectroscopía infrarroja de óptica difusa -near infrared diffuse optical spectroscopy (NIRS)- y espectroscopía de correlación de luz difusa -diffuse correlation spectroscopy (DCS)-. Estos híbridos permiten la medición simultánea de la concentración de hemoglobina total en sangre, la saturación de oxígeno y el flujo sanguíneo. En un estudio preclínico, apliqué el dispositivo híbrido para monitorizar la respuesta de carcinomas de células renales, implantados en ratones, a terapias antiangiogénicas. Los resultados sugieren que podemos predecir la evolución de la terapia con base en cambios hemodinámicos tempranos, lo cual proporciona información valiosa para un mejor entendimiento del mecanismo de resistencia de los tumores a las terapias antiangiogénicas. En dos estudios in vivo realizados en pacientes voluntarios, desarrollé protocolos y sondas para demostrar la viabilidad de la espectroscopía de óptica difusa no invasiva en el estudio de la patofisiología ósea. El primer estudio se concentró en la fisiología microvascular de la rótula y en el otro se muestra que el manubrio, hueso rico en médula ósea roja, es un sitio accesible para la óptica difusa, y se presenta como una ventana para monitorizar la progresión de enfermedades hematológicas malignas. En resumen, durante mi trabajo doctoral, desarrollé instrumentación, algoritmos y protocolos que posteriormente apliqué en estudios preclínicos y clínicos. Mi trabajo de investigación constituye así un enlace entre estos estudios y abre nuevas áreas de aplicación en oncología.

After an intense development of optical tweezers as a biophysical tool during the last decades, quantitative experiments in living cells have not found in this technique its best ally, due, in part, to the lack of a reliable method to measure forces in complex environments. The attempts to overcome this problem either require complicated in situ calibrations, which make their use impossible in the study of dynamic processes, or they are inaccurate. Using a different approach, Steven Smith at Carlos Bustamante’s lab at the University of Berkeley developed a method based on the direct measurement of the momentum change of the trapping beam. However, its diffusion has been modest mainly because it requires a counter-propagating optical trapping system, which is difficult to implement and combine with other techniques. Although it has not been used for this purpose yet, it seems a more suitable method for in vivo experiments since the measurement depends only on some properties of the sensor apparatus but not on the experiment itself. On the other hand, the use of holographic optical tweezers in molecular biology experiments involving force and position measurements is still far from established. The existence of different effects associated to the use of spatial light modulators to create the optical traps has restricted their use. In this thesis, I present the work that I carried out in the Optical Trapping Lab – Grup de Biofotònica at the University of Barcelona related to these two subjects. During these years, I have focused on the implementation of the force detection method based on the conservation of the light momentum in single-beam optical traps, and on the analysis of several aspects of holographic tweezers oriented to their use in quantitative experiments.