Thèses

Mercredi 8 Décembre 2021 à 10h00.

Self-assembled permanent micromagnets for the isolation of Circulating Tumor Cells in a microfluidic device

''Circulating tumor cells (CTCs) have received significant attention over years for their potential clinical significance. The isolation of CTCs directly from blood, as a liquid biopsy, could serve for early cancer diagnosis, patient outcome prognosis, and treatment efficacy monitoring, paving the way for personalized cancer medicine. Microfluidic devices have emerged as promising tools to isolate CTCs since they offer precise cell manipulation, versatile functions, and cost-effective fabrication. In this thesis, we developed a microfluidic device integrating dense arrays of permanent micro-magnets that can isolate viable and pure CTCs from whole blood for downstream characterization. We reported an original fabrication approach, based on magnetic polymer composites, breaking with standard microfabrication techniques. Micro-magnets were obtained by microstructuring a mixture of NdFeB microparticles and PDMS, which leads to the self-organization of magnetic particles due to dipoledipole interactions. We further characterized the micro-magnets, which revealed a high aspect ratio structure and generated magnetic forces up to several nanoNewtons at their surface. The micromagnets, acting like micro-traps, were implemented for CTC isolation by performing white blood cell depletion. We used cancer cell lines (A549, MCF-7) as CTC models and demonstrated their successful recovery, while preserving their viability for subsequent analyses, including cell culture, phenotypic and genotypic studies. Finally, the magnetophoretic device was combined with a size-based separation technology to achieve high purity, therefore meeting the needs of clinicians.

Directeurs de thèse :
Anne-Laure DEMAN (INL), Damien LE ROY(iLM)

Membres du jury / members of the jury:
DEN TOONDER Jaap, Professeur, Université technique d’Eindhoven (Rapporteur)
LE PIOUFLE Bruno, Professeur des universités, ENS Cachan (Rapporteur)
FERRIGNO Rosaria, Professeure des universités, Université Lyon 1 (Examinatrice)
RAILLON Camille, Ingénieure de recherche, CEA Grenoble (Examinatrice)
DEMAN Anne-Laure, Maître de conférence, INL (Directrice de thèse)
LE ROY Damien, Maître de conférence, ILM (Co-encadrant de thèse)
PAYEN Léa, Professeure des Universités-Praticien Hospitalier (Invitée)

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