Ultrasensitive microfluidic detection of red blood cell deformability: Age-related decline in deformability

Red blood cell (RBC) deformability is closely linked to aging and holds promise as an indicator of biological age. However, current hematological techniques lack the sensitivity to accurately discern the subtle differences in deformability associated with aging. To overcome this limitation, we developed an ultrasensitive microfluidic device inspired by the spleen's filtration mechanism. The device features a porous section created by packing 25 μm beads into a tube with a diameter of 400 μm and a length of 2 mm. RBCs with higher deformability traverse this porous region more rapidly, covering longer distances and achieving higher velocities. Hematocrit levels were meticulously standardized to ensure measurement consistency. In murine models, statistically significant differences in RBC deformability were observed across age groups (1, 6, 12, and 18 months). For human samples, cell aggregation was minimized by diluting the specimens to approximately 60% and adjusting the osmolarity to 170 mOsm, which allowed for a clear distinction in deformability between the young group (median age: 30 years, range: 12-40 years) and the older group (median age: 72 years, range: 65-90 years). Using a cutoff speed of 0.9 mm/s to differentiate the two groups, the diagnostic performance demonstrated an area under the curve of 0.84, a sensitivity of 78.3%, and a specificity of 73.9%, indicating moderate diagnostic accuracy. These findings confirm that RBC deformability is a reliable marker for age-related physiological changes, and the method could be further applied to estimate physiological age, assess systemic aging, and evaluate oxygen delivery efficiency.