Microfluidic Chip Platforms for Red Blood Cell Storage Lesion Quality Control and Precision Transfusion

Red blood cell (RBC) transfusion is a core clinical intervention. However, hypothermic storage induces progressive biochemical, structural, and functional impairments collectively termed the RBC storage lesion (RSL), which compromises post-transfusion efficacy and safety. Conventional RSL detection relies on bulk population-averaged indicators with low physiological relevance and no single-cell resolution, failing to capture cellular heterogeneity and microcirculatory dysfunction. Lab-on-a-chip (LOC) platforms are established with microfluidic technology, and organ-on-a-chip represents a biomimetic and advanced extension of such systems. Together, they enable biomimetic reconstruction of the in vivo microcirculatory microenvironment, high-throughput single-cell analysis, and quantitative assessment of RBC mechanical phenotypes under physiological shear conditions. Distinct from fragmented prior reviews that separate microfluidic engineering from transfusion clinical demands, this work systematically outlines the molecular mechanisms and clinical impacts of RSL alongside unresolved detection bottlenecks, and builds an integrated LOC-endothelium-on-a-chip technical framework covering structural design, biocompatible material screening, and standardized fabrication workflows. It further summarizes microfluidic core applications including single-cell deformability quantification, stiffness evaluation, hemolysis susceptibility testing, microvascular occlusion simulation, and RBC-endothelial interaction analysis. Uniquely, it constructs a tiered translational roadmap integrating microfluidics with multi-omics, artificial intelligence, vascularized multi-organ chips, and function-centered pre-transfusion surveillance, and proposes microfluidic strategies to optimize RBC storage regimens. In summary, microfluidic technology overcomes the limitations of conventional assays for RSL quality control, provides an emerging technical platform for RSL mechanistic research, pretransfusion quality evaluation, and donor-specific precise matching, and promotes the transformation of transfusion medicine from time-based empirical management to function-oriented precision practice.