FlowMorph: Physics-Consistent Self-Supervision for Label-Free Single-Cell Mechanics in Microfluidic Videos

Abstract: Mechanical properties of red blood cells (RBCs) are promising biomarkers for hematologic and systemic disease, motivating microfluidic assays that probe deformability at throughputs of $10^3$--$10^6$ cells per experiment. However, existing pipelines rely on supervised segmentation or hand-crafted kymographs and rarely encode the laminar Stokes-flow physics that governs RBC shape evolution. We introduce FlowMorph, a physics-consistent self-supervised framework that learns a label-free scalar mechanics proxy $k$ for each tracked RBC from short brightfield microfluidic videos. FlowMorph models each cell by a low-dimensional parametric contour, advances boundary points through a differentiable ''capsule-in-flow'' combining laminar advection and curvature-regularized elastic relaxation, and optimizes a loss coupling silhouette overlap, intra-cellular flow agreement, area conservation, wall constraints, and temporal smoothness, using only automatically derived silhouettes and optical flow. Across four public RBC microfluidic datasets, FlowMorph achieves a mean silhouette IoU of $0.905$ on physics-rich videos with provided velocity fields and markedly improves area conservation and wall violations over purely data-driven baselines. On $\sim 1.5\times 10^5$ centered sequences, the scalar $k$ alone separates tank-treading from flipping dynamics with an AUC of $0.863$. Using only $200$ real-time deformability cytometry (RT-DC) events for calibration, a monotone map $E=g(k)$ predicts apparent Young's modulus with a mean absolute error of $0.118$\,MPa on $600$ held-out cells and degrades gracefully under shifts in channel geometry, optics, and frame rate.