Table 1:

Examples of microfluidics models applied for investigation of sickle RBC biophysical properties

Model Type	Measurements	Findings	References
Microvasculature-on-a-chip	Transit time Time to occlusion Adherent sickle cells Platelet and fibrin deposition	Endothelial-sRBC interactions and geometry contribute to vaso-occlusion	Carden et al. 2017. Microcirculation Carden et al. 2017 Blood Mathur et al. 2021. Bioeng Transl Med
Oxygen-Tension modulation Microvasculature model Shear-thinning	Oxygen-dependent velocity Oxygen-dependent rheology Oxygen-gradient and vascular size Oxygen-dependent viscosity changes	Sickle Hb concentration increases blood viscosity with decreasing oxygen tension	Wood et al. 2012. Sci Transl Med Lu et al. 2018. Am J Hematol Valdez et al. 2019. APL Bioeng
Single-RBC Hemoglobin polymer content	Measurement of single-RBC Hb polymer	Semi-quantitative measurement of hemoglobin polymer in single RBCs as function of oxygen	DiCaprio et al. 2019. PNAS
Red cell biomechanics and rheology	Sickling kinetics Image-based quantification of SRBC deformity RBC cortical tension Splenic-like slit device pH and oxygen associated biomechanics sRBC behavior in cycles of hypoxia	Cortical tension in sRBC and pH increase stiffness of RBCs Shape-dependent velocities are important.	Abbyad et al. 2010. Lab Chip Guraprasad et al. 2019. Am J Hematol. Li et al. 2017. PLoS Comput. Biol. Gambhire, P et al. 2017. Small Guo et al. 2014. J Biomech. Du E. and Dao M. 2019. Exp Mech.
RBC adhesion	Flow dependent RBC adhesion to laminin and fibronectin RBC deformability	Sickle RBC adhesion to endothelial ligands or activated endothelium	Alapan et al. 2014. Scientific Rep Alapan et al. 2016. Transl Res Kucukal et al. 2018. Am J Hem
OcclusionChip Microfluidic electrical impedance	RBC-mediated microvascular occlusion	Percent occlusions and percent impedance change across device correlates with HbS phenotype	Man et al. 2021. Microcirculation Man et al 2021. Lab Chip Liu et al. 2018. Phys Fluids.
Pulsatile parallel plate flow adhesion	Sickle RBC adhesion to VCAM-1, Laminin	Sickle RBC adhesion to endothelial ligands or activated endothelium can be blocked by antibodies	White J et al. 2015. Clin Hemorheol Microcirc