<p dir="ltr">The emergence of infectious diseases like HIV, influenza, and COVID-19 highlights the urgent need for highly scalable testing methods that can be deployed outside traditional laboratory settings. Despite decades of research in point-of-care (POC) diagnostics, the main challenge remains the limited performance of assays, especially in terms of sensitivity. Furthermore, most POC assays originating from academic research struggle to transition beyond the laboratory due to manufacturability issues. This dissertation aims to enhance the effectiveness of viral molecular detection platforms for POC diagnostics by improving analytical and clinical sensitivity and facilitating the practical adaptation of academic-developed POC devices for use outside laboratory settings.</p><p dir="ltr">Each aim addresses a separate aspect of device development. The first aim addresses the need for clinical accuracy during test interpretation, especially in POC or at-home diagnostic tests, by developing an internal amplification control (IAC). Here, I develop a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for detecting SARS-CoV- 2 along that incorporates a housekeeping gene as an IAC to ensure the quality of collected samples and the validity of assay reagents. The valid results can be easily visualized in triple-line lateral flow immunoassay (LFIA). The second aim makes progress towards overcoming the limited analytical sensitivity of existing rapid diagnostic tests for acute HIV infection screening. Here, I introduce a novel antibody-initiated LAMP assay targeting the HIV p24 capsid protein that combines LAMP sensitivity with the specificity of HIV p24 and its antibody. There are 3000 p24 capsid proteins present in the virion compared to only 2 viral RNA copies. In the assay, two DNA- conjugated antibody probes will each bind to p24 and their proximity will allow the DNA overlaps to generate a complete DNA target that acts as a trigger for the LAMP reaction. An LFIA is integrated into this design to enable simple result visualization. The third aim improves manufacturability and assembly of our existing nucleic acid detection platform by simplifying the platform components while maintaining the user-friendly sample-to-answer concept. Here, I validate material compatibility testing, assess chamber fabrication methods amenable to large-scale manufacturing, evaluate alternative heating units, and examine fluid flow control mechanisms of the redesigned wax valve. These combined aims demonstrate promising outcomes for practical implementation of molecular diagnostics to the POC.</p>

Ce travail de thèse expérimental traite de la caractérisation et de l'optimisation de sources d'électrons et de photons (gamme en énergie keV- MeV) produites lors de l'interaction d'un laser à impulsion courte et intense avec une cible à l'état de plasma. La caractérisation en énergie et angulaire de ces sources est un enjeu d'importance, notamment dans la perspective de les utiliser pour des expériences de physiques nucléaires dans les plasmas. Une partie de ce travail est consacrée à l'étude des écrans photostimulables (IPs), détecteurs couramment utilisés pour la mesure des distributions en énergie et angulaire des faisceaux de particules accélérées par laser. Les caractéristiques des écrans de type MS, SR et TR de la marque Fuji ont été étudiés et leurs fonctions de réponse aux électrons, photons, protons et particules alpha sont établies dans une gamme en énergie de quelques kev à plusieurs MeV. Enfin un protocole est proposé pour réaliser des mesures quantitatives avec ces détecteurs dans différentes configurations expérimentales.Dans une seconde partie, une source d'électrons produite avec l'installation ELFIE du LULI dans la gamme en énergie de l'ordre du MeV a été caractérisée et optimisée en faisant varier l’extension spatiale du pré-plasma dans lequel interagi le laser intense. En particulier nous montrons que plus de 1011 électrons de plus de 10 MeV sont accélérés lors de l’interaction laser- plasma pour des conditions particulières d’extension longitudinale du pré-plasma en amont, mais aussi en aval de la cible.Dans une dernière partie, une source de photons produite à haute cadence avec le laser AURORE du CELIA est étudiée dans une gamme en énergie d'une dizaine de keV. L’originalité de la source réside dans la nature de la cible qui est du gallium à l'état liquide. Nous montrons en particulier que l'énergie moyenne et le nombre des photons peuvent être optimisés en créant des jets de gallium à la surface de la cible au moyen d'une pré-impulsion laser. Une interprétation physique du phénomène est proposée s’appuyant sur des simulations numériques. / This work takes place in the framework of the characterization and theoptimization of laser-driven electron and photon sources. With the goal of usingthese sources for nuclear physics experiments, we focused on 2 energy ranges:one around a few MeV and the other around a few tens of keV. The first partof this work is thus dedicated to the study of detectors routinely used forthe characterization of laser-driven particle sources: Imaging Plates. A modelhas been developed and is fitted to experimental data. Response functions toelectrons, photons, protons and alpha particles are established for SR, MS andTR Fuji Imaging Plates for energies ranging from a few keV to several MeV. Thesecond part of this work present a study of ultrashort and intense electron andphoton sources produced in the interaction of a laser with a solid or liquid target.An experiment was conducted at the ELFIE facility at LULI where beams ofelectrons and photons were accelerated up to several MeV. Energy and angulardistributions of the electron and photons beams were characterized. The sourceswere optimized by varying the spatial extension of the plasma at both the frontand the back end of the initial target position. In the optimal configuration ofthe laser-plasma coupling, more than 10exponent11 electrons were accelerated. In the caseof liquid target, a photon source was produced at a high repetition rate on anenergy range of tens of keV by the interaction of the AURORE Laser at CELIA(10exponent16 W cm exponent-2) and a melted gallium target. It was shown that both the meanenergy and the photon number can be increased by creating gallium jets at thesurface of the liquid target with a pre-pulse. A physical interpretation supportedby numerical simulations is proposed.

The Multidisciplinary University Research Initiative (MURI) research at Texas A and M University is concerned with the experimental characterization of non-thermal and non-chemical equilibrium systems in hypersonic (Mach greater than 5) flowfields using experimental diagnostics, and is an interdisciplinary collaboration between the Chemistry and Aerospace Engineering departments. Hypersonic flight conditions often lead to non-thermochemical equilibrium (NTE) state of air, where the timescale of reaching a single (equilibrium) Boltzmann temperature is much longer than the timescale of the flow, meaning that certain molecular modes such as vibrational modes, may be much more excited than the translational or rotational modes of the molecule leading to thermal-nonequilibrium. A nontrivial amount of energy is therefore contained within the vibrational mode, and this energy cascades into the flow as thermal energy, affecting flow properties through the process of various vibrational-vibrational (V-V) and vibrational-translational (V-T) energy exchanges between the flow species. The research is a fundamental experimental study of these NTE systems and involves the application of advanced laser and optical diagnostics towards hypersonic flowfields. The research is broken down into two main categories: the application and adaptation of existing laser and optical techniques towards characterization of NTE, and the development of new molecular tagging velocimetry techniques which have been demonstrated in an NTE flowfield, but may be extended towards a variety of flowfields.