A particulate blood-mimicking fluid with physiological biconcave geometry for microscale hemorheology

Blood exhibits complex flow behavior governed by red blood cell (RBC) deformation, aggregation, and confinement effects, which are difficult to reproduce in vitro at single-cell level under confinement. Existing blood mimicking fluids (BMFs) primarily replicate bulk rheology but fail to capture microscale single-cell mechanics relevant to microcirculation. Here, we present a particulate blood mimicking fluid (BMF) composed of monodisperse hydrogel-based artificial erythrocytes (ARBC) with a physiological diameter of 9 μm, biconcave geometry, and plasma-phase-dependent mechanical properties. ARBCs are generated using a cross-flow microfluidic fabrication approach, enabling reproducible fabrication and integration into well-defined plasma-phase analogues. Adjustment of the surrounding plasma-phase analogue enabled modulation of particle swelling, elasticity, and interparticle interactions. Under confined microchannel flow, particles exhibited velocity-dependent deformations from disc-like to bullet-like morphologies, reproducing the characteristic trend observed for human RBCs. Depending on the plasma-phase composition, measured deformation indices overlapped with those obtained for RBCs under comparable confinement conditions. By combining physiological geometry, elasticity, and controllable plasma-phase properties, this platform provides a standardized model system for studying microscale hemorheology and for validating deformation-based lab-on-a-chip technologies.