Thesis presented February 01, 2022

Abstract:
In the context of the improvement of medical biology analysis processes and particularly of diagnostic methods, extracellular vesicles appear as biomarkers with a strong potential since about ten years. They indeed carry the protein signature of their emitting cells, which can be exploited as a diagnostic tool. However, the scientific community is facing a lack of technological tools for these biomarkers isolation due to the heterogeneity of the sample of nanometric-scale particles. These limitations hinder the use of these new types of biomarkers in clinical diagnosis. Thus, new methods are required to perform efficient, simple and rapid isolation of extracellular vesicles from liquid biopsy.
The development of a system using new technologies at the frontier of the fields of microfluidics and biochemistry is part of this evolution. The microfluidic technique of Deterministic Lateral Displacement (DLD) size sorting appears to be one of the promising technologies for the passive sorting of biological objects. The combination of size sorting and biomarker-specific sorting is then enabled by the combination of a DLD system coupled to aptamers targeting biomarker proteins of interest. The possibilities of specific capture of extracellular vesicles by aptamers have been studied as alternative probes to antibodies by setting up a new detection method. In parallel, the development of a DLD-based microfluidic system for the isolation of extracellular vesicles from complex biological media as an alternative to conventional methods has been performed. The integration of biomarker-specific DLD sorting using aptamers has been addressed in order to propose a complete microfluidic system for the analysis of extracellular vesicles from biofluids.

Keywords:
Extracellular vesicles, Microfluidics, Aptamers, DLD, Biomarkers, Cancer

On-line thesis.