Fluorescence microscopy has revolutionized medicine and biological science with its ability to study the behavior and chemical expressions of living cells. Fluorescent probes can label cell components or cells of a particular type. Clinically the impact of fluorescence imaging can be seen in the diagnosis of cancers, AIDS, and other blood related disorders. Although fluorescence imaging devices have been established as a vital tool in medicine, the size, cost, and complexity of fluorescence microscopes limits their use to central laboratories. The work described in this thesis overcomes these limitations by developing a low cost integrated fluorescence microscope so single use fluorescence microscopy assays can be developed. These assays will enable at-home testing, diagnostics in resource limited settings, and improved emergency medicine.

Les travaux effectués au cours de cette thèse concernent le développement d’un instrument à faible coût et porté sur la personne permettant le suivi quantitatif des paramètres physiologiques de la peau in vivo et de manière non invasive. L’instrument est fondé sur la technique de Spectroscopie de Réflectance Diffuse résolue spatialement (srDRS). Cette technique fournit une quantification absolue des propriétés optiques endogènes d’absorption et de diffusion du tissu sondé et possède un potentiel pour la caractérisation de ces propriétés en couches de la peau.Afin de maximiser ce potentiel, notre approche repose sur l’utilisation d’un capteur matriciel placé en contact avec le tissu et permettant l’imagerie de réflectance diffuse à haute résolution spatiale. Les travaux présentés ici comprennent la spécification et la validation d’une architecture innovante permettant la mise en œuvre de l’approche proposée, l’implémentation d’un système porté sur la personne et bas coût basé sur cette architecture et l’évaluation des performances de ce système au travers d’expérimentations à la fois sur fantômes de peau et in vivo. Les résultats obtenus valident le potentiel de l’instrument développé pour le suivi quantitatif et non-invasif des propriétés de la peau. L’approche proposée est prometteuse pour l’analyse de milieux en couches tels que la peau et ouvre la voie au développement d’une nouvelle génération d’instruments portés sur la personne et bas coûts pour le suivi en continu des propriétés optiques des tissus. / This work presents the development of a low-cost, wearable instrument for quantitative monitoring of skin physiological parameters toward non-invasive diagnostics in vivo. The instrument is based on the spatially resolved Diffuse Reflectance Spectroscopy (srDRS) technique, which provides absolute quantification of absorption and scattering endogenous properties of the probed tissue volume with a potential to discriminate between properties of individual skin layers. In the developed instrument, this potential is maximized by the use of a multi-pixel image sensor to perform contact, high resolution imaging of the diffuse reflectance. This study comprises the specification and validation of a novel srDRS system architecture based on the proposed approach, the implementation of this architecture into a low-cost, wearable device and the evaluation of the device performance both on tissue-simulating phantoms and in vivo. Results validate the potential of the instrument for the non-invasive, quantitative monitoring of tissue properties. The described approach is promising for addressing the analysis of layered tissue suchas skin and paves the way for the development of low-cost, wearable devices for continuous, passive monitoring of tissue optical properties.

La mise en glissement d’une interface de contact est un phénomène dont la dynamique spatiotemporelle est encore mal comprise. Dans cette thèse, nous avons développé et mis en oeuvre un dispositif expérimental original permettant de visualiser in situ les phénomènes locaux en jeu lors de la mise en glissement d’interfaces rugueuses élastomères, avec une bonne résolution temporelle. Nous avons mis en évidence une forte réduction de l’aire de contact réelle au sein d’une interface de contact sous cisaillement, et ce bien avant le début du glissement macroscopique. Cette réduction influence la valeur de la force de frottement statique de l’interface. Nous avons montré que le paramètre qui quantifie l’amplitude de la réduction vérifie une loi d’échelle valable largement, allant des monocontacts millimétriques jusqu’aux jonctions micrométriques impliquées dans les interfaces rugueuses. Nous avons ensuite montré que la contrainte de cisaillement critique de mise en glissement d’une interface n’est pas une constante pour un couple de matériaux en contact. En effet, en changeant systématiquement l’épaisseur d’un revêtement élastique sur l’un des corps en contact, on peut varier cette contrainte d’un facteur trois. Cet effet est interprété semi-quantitativement via un modèle couplant dissipation à l’interface et dans le volume des matériaux. Nous avons enfin montré que la dynamique spatio-temporelle de mise en glissement est influencée par le couple appliqué à l’interface par la force de frottement, lorsque celle-ci n’est pas exercée dans le plan de l’interface. En particulier, via une mesure du champ de déplacement par corrélation d’images, nous avons réalisé la première comparaison quantitative avec un modèle récent décrivant cet effet de couple. / The onset of sliding of a contact interface is a phenomenon the space-time dynamics of which are still poorly understood. In this thesis, we have developed and implemented an original experimental device allowing us to visualize in situ the local phenomena involved during the onset of sliding of rough elastomer interfaces, with a good temporal resolution. We have shown a strong reduction of the real contact area within a sheared contact interface, well before the beginning of macroscopic sliding. This reduction affects the value of the static friction force of the interface. We have shown that the parameter that quantifies the amplitude of the reduction obeys a well-defined scaling law ranging from millimetric mono-contacts to the micrometric junctions involved in rough interfaces. We have then shown that the shear strength of an interface is not a constant for a couple of materials in contact. Indeed, by systematically changing the thickness of an elastic coating on one of the bodies in contact, we could vary the value of the shear strength by a factor three. This effect is interpreted semi-quantitatively via a model incorporating dissipation both at the interface and in the bulk of the materials. We have finally shown that the space-time dynamics of the onset of sliding is influenced by the torque applied to the interface by the friction force, when the latter is not exerted in the plane of the interface. In particular, via a digital image correlation-based measurement, we performed the first quantitative comparison with a recent model describing this torque effect.

Les enjeux de consommation d'énergie et de sécurité ont fait du frottement entre les pneumatiques et la chaussée une propriété importante lors de la conception de nouveaux pneumatiques. Pour mesurer ces efforts de frottement deux cinématiques sont couramment utilisées : la mise en glissement et le roulement/glissement. Les lois de frottement issues des expériences de mise en glissement sont assez bien interprétées. En revanche, le lien qui existe entre ces lois de frottement et le comportement en roulement/glissement est encore mal compris. En particulier, les modèles de roulement/glissement n'incorporent pas la transition entre frottement statique et frottement dynamique, bien que cette phénoménologie soit bien établie expérimentalement. Dans cette thèse, nous proposons différents modèles de frottement en roulement/glissement qui étendent ceux de la littérature en intégrant explicitement la transition de frottement statique/dynamique. Pour tester ces modéles dans le cas du contact pneu/chaussée, nous avons réalisé des expériences selon les deux cinématiques, sur un contact simplifié élastomère/chaussée. A partir des expériences de mise en glissement, les paramètres de la loi de frottement sont identifiés, en fonction de la force normale appliquée, de la vitesse de glissement et de la nature de la chaussée. Ces résultats sont implémentés dans nos modèles, pour produire des prédictions en roulement/glissement, qui sont finalement comparées avec les mesures obtenues en roulement/glissement. De plus, certaines hypothèses des modèles ont été testées par des expériences de visualisation in situ du contact. En particulier nous confirmons, sur une interface élastomère/verre, la présence simultanée d'une zone collée et d'une zone en glissement en conditions de roulement/glissement. / For safety and energy consumption issues, tyre friction has become an important property when designing tyres. There are two main kinematic conditions which are commonly used to measure friction forces : the onset of sliding and the rolling/sliding. The friction laws which are extracted from the onset of sliding experiments are rather well interpreted. In contrast, the link between those frictions laws and the rolling/sliding behaviour remains incompletely understood. In particular, the rolling/sliding models do not take into account the transition between static friction and dynamic friction, although it is a well-established phenomenology. In this manuscript, we propose diérent models of friction in rolling/sliding, which extend those of the literature by explicitly integrating a static/dynamic friction transition. To test these models in the case of a tyre/road contact, we performed experiment in the two kinematic conditions, on a simpliéd elastomer/road contact. From the onset of sliding experiments, we identify the parameters of the friction law as functions of the applied normal force, the sliding speed and the type of road. These results are used as inputs in our models to predict the rolling/sliding behaviour, and are eventually compared with the corresponding experiments. In addition, we have tested several assumptions made in the models by performing in situ contact imaging experiments. In particular we con_rm, on an elastomer/glass interface, the simultaneous presence of a sticking and a slipping zone in rolling/sliding conditions.

Within the realm of biosensing, DNA analysis has become an indispensable research tool in medicine, enabling the investigation of relationships among genes, proteins, and drugs. Conventional DNA microarray technology uses multiple lasers and complex optics, resulting in expensive and bulky systems which are not suitable for point-of-care medical diagnostics. The immobilization of DNA probes across the microarray substrate also results in substantial spatial variation. To mitigate the above shortcomings, this thesis presents a set of techniques developed for the CMOS image sensor for point-of-care spectrally-multiplexed fluorescent DNA sensing and other fluorescence biosensing applications. First, a CMOS tunable-wavelength multi-color photogate (CPG) sensor is presented. The CPG exploits the absorption property of a polysilicon gate to form an optical filter, thus the sensor does not require an external color filter. A prototype has been fabricated in a standard 0.35μm digital CMOS technology and demonstrates intensity measurements of blue (450nm), green (520nm), and red (620nm) illumination. Second, a wide dynamic range CMOS multi-color image sensor is presented. An analysis is performed for the wide dynamic-range, asynchronous self-reset with residue readout architecture where photon shot noise is taken into consideration. A prototype was fabricated in a standard 0.35μm CMOS process and is validated in color light sensing. The readout circuit achieves a measured dynamic range of 82dB with a peak SNR of 46.2dB. Third, a low-power CMOS image sensor VLSI architecture for use with comparator based ADCs is presented. By eliminating the in-pixel source follower, power consumption is reduced, compared to the conventional active pixel sensor. A 64×64 prototype with a 10μm pixel pitch has been fabricated in a 0.35μm standard CMOS technology and validated experimentally. Fourth, a spectrally-multiplexed fluorescence contact imaging microsystem for DNA analysis is presented. The microsystem has been quantitatively modeled and validated in the detection of marker gene sequences for spinal muscular atropy disease and the E. coli bacteria. Spectral multiplexing enables the two DNA targets to be simultaneously detected with a measured detection limit of 240nM and 210nM of target concentration at a sample volume of 10μL for the green and red transduction channels, respectively.

Within the realm of biosensing, DNA analysis has become an indispensable research tool in medicine, enabling the investigation of relationships among genes, proteins, and drugs. Conventional DNA microarray technology uses multiple lasers and complex optics, resulting in expensive and bulky systems which are not suitable for point-of-care medical diagnostics. The immobilization of DNA probes across the microarray substrate also results in substantial spatial variation. To mitigate the above shortcomings, this thesis presents a set of techniques developed for the CMOS image sensor for point-of-care spectrally-multiplexed fluorescent DNA sensing and other fluorescence biosensing applications. First, a CMOS tunable-wavelength multi-color photogate (CPG) sensor is presented. The CPG exploits the absorption property of a polysilicon gate to form an optical filter, thus the sensor does not require an external color filter. A prototype has been fabricated in a standard 0.35μm digital CMOS technology and demonstrates intensity measurements of blue (450nm), green (520nm), and red (620nm) illumination. Second, a wide dynamic range CMOS multi-color image sensor is presented. An analysis is performed for the wide dynamic-range, asynchronous self-reset with residue readout architecture where photon shot noise is taken into consideration. A prototype was fabricated in a standard 0.35μm CMOS process and is validated in color light sensing. The readout circuit achieves a measured dynamic range of 82dB with a peak SNR of 46.2dB. Third, a low-power CMOS image sensor VLSI architecture for use with comparator based ADCs is presented. By eliminating the in-pixel source follower, power consumption is reduced, compared to the conventional active pixel sensor. A 64×64 prototype with a 10μm pixel pitch has been fabricated in a 0.35μm standard CMOS technology and validated experimentally. Fourth, a spectrally-multiplexed fluorescence contact imaging microsystem for DNA analysis is presented. The microsystem has been quantitatively modeled and validated in the detection of marker gene sequences for spinal muscular atropy disease and the E. coli bacteria. Spectral multiplexing enables the two DNA targets to be simultaneously detected with a measured detection limit of 240nM and 210nM of target concentration at a sample volume of 10μL for the green and red transduction channels, respectively.