Investigating Hemorheology via Microfluidics: Red Blood Cell Aggregation and Mechanics

The dynamics of red blood cells (RBCs) in circulation are central to understanding blood flow and its broader implications for health and disease, necessitating innovative approaches to study their behavior under physiological and pathological conditions. The efficiency of the intricate human circulatory system is profoundly influenced by both the collective and individual behavior of RBCs. Aggregation, a key factor in blood rheology and microcirculatory flow, is governed by mechanical properties and cell aggregability.
This thesis investigates RBC aggregate dissociation in extensional flow using hyperbolic microfluidic constrictions and CNN-based image analysis. It examines extensional stress in destabilizing aggregates of varying strengths and the impact of RBC density—linked to cell age and mechanics—on aggregability. Results show a sharp increase in dissociation beyond a critical extension rate, with denser, aged RBCs forming more stable aggregates. Percoll gradient centrifugation clarifies the interplay between aging, mechanics, and aggregation, offering experimental validation for theoretical models and clinical blood rheology assessment.
The developed microfluidic device was applied in a clinical study with CHU Grenoble Alpes to assess RBC deformability as a biomarker for disease and patient monitoring. Initial findings confirm its sensitivity to pathological mechanical alterations.
Additionally, this research contributes to an ESA-sponsored study on blood rheology changes in microgravity, addressing circulation anomalies observed in astronauts. A prototype, tested in CNES and ESA parabolic flights, suppresses sedimentation and characterizes RBC aggregation dynamics under slow flow using viscosity measurements and optical analysis. Insights from moderate shear rates inform future space experiments.
The findings from the thesis deepen the understanding of blood rheology in physiological and pathological contexts and offer potential translational applications in clinical diagnostics and patient care. These insights highlight the interplay between cellular mechanics, aggregation behavior, flow conditions, and physico-chemical factors, providing valuable directions for future studies in blood flow and microcirculation.

Thèse de doctorat dirigée par M. Thomas Podgorski, LRP Grenoble

Devant un jury composé de :

• M. Manouk Abkarian, Cbs Montpellier - Rapporteur
• Mme Magalie Faivre, INL Lyon - Rapporteure
• Mme Sylvie Lorthois, IMFT Toulouse - Examinatrice
• M. Hugues Bodiguel, LRP Grenoble - Examinateur