Development of a micro-tissue analysis microsystem by microweve dielectric spectroscopy for the real-time evaluation of biological effects of chemical agents ; Développement d'un microsystème d'analyse de micro-tissus par spectroscopie diélectrique hyperfréquence pour l'évaluation en temps réel d'effets biologiques d'agents chimiques

National audience ; Microwave dielectric spectroscopy is a promising analytical technique for many fields of application, especially cell biology. It allows to study cells in their culture medium in a non-invasive and non-destructive way thanks to their dielectric properties. This can be done at various scales, from organ or tissue, from cell suspensions to single cell analysis. In addition, there is an intermediate scale not yet approached with such an analysis technique, that of micro-tissues or spheroids, a highly prized in vitro biological model because it is close to the problems encountered in vivo. These are clusters of cells aggregated together, which present different gradients, both in composition and environment. The cells are in contact with each other and form a sphere, hence the term 3D model or spheroid. The aim of this thesis is to extend the capabilities of cellular analysis by dielectric microwave spectroscopy to this new scale, that of micro-tissues. This work follows a first demonstrator previously developed in the MH2F research team of LAAS. This first Radiofrequency (RF) microsensor adapted to the microwave measurement of spheroids of 300 µm diameter maintained in their culture medium by an open fluidic system of the reservoir type had been designed, manufactured and started to be evaluated beforehand. In addition to further characterization of this component using multiple models, polystyrene beads and spheroids, to define its measurement capabilities and limitations, an electrical model to obtain the dielectric parameters of the object under study was developed. Thus, after having introduced the spheroids as a biological model and the various existing characterization techniques of this type of model in a first chapter, the second chapter is dedicated to the introduction of this first demonstrator and its analysis capacities. Different solutions were then considered in order to overcome these limitations, including making the fluidic configuration closed in association with a blocking ...