Document Type
Article
Publication Date
1-21-2026
Abstract
Emerging therapies in sickle cell disease (SCD) aim to restore healthy red blood cell (RBC) function, but they often yield heterogeneous cellular responses. There are no proven techniques to evaluate restored rheological functionality and heterogeneity in these RBCs. We present a biomimetic microcapillary network, high-speed imaging, and computational algorithms to analyze RBC capillary velocity profiles of the entire sample population at single-cell resolution. Using peripheral RBCs from SCD patients and healthy donors, we showed that RBC capillary transit velocity correlated with cell shape, hydrodynamic adaptability, and elongation index. Healthy RBCs exhibited a velocity distribution skewed toward higher values, whereas RBCs from individuals with SCD showed a shift toward lower velocities. SCD samples had a greater fraction of slow RBCs than healthy controls (42.1% ± 12.0% vs. 19.0% ± 4.9%, p < 0.0001). We tested mixtures of healthy and SCD RBCs to simulate heterogeneous therapeutic effects and demonstrated that the assay was sensitive to small fractions of abnormal RBCs. The slow RBC fraction emerged as a potential biomarker associated with SCD disease severity. This fraction significantly increased under hypoxia showing sensitivity to hypoxia-induced sickling. Finally, we assessed in vitro-derived RBCs and observed distinct velocity profiles for nucleated and enucleated cells. Processing methods to enrich enucleated RBCs improved the velocity profile, producing a distribution that was more comparable to that of peripheral RBCs. This platform's ability to assess individual RBCs and generate a velocity profile from a small number of cells makes it well suited for evaluating the rheological properties of in vitro-derived RBCs.
Language
English
Publication Title
Lab on A Chip
Grant
D43TW012260
Rights
© 2026 The Author(s). This is an open access work distributed under the terms of the Creative Commons Attribution-Non-Commercial (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Solomon Oshabaheebwa, Utku Goreke, Yuxuan Du, Christopher L. Wirth, Zoe Sekyonda, Bryan L. Benson, Payam Fadaei, Yusang B. Ley, Nathan M. Perez, Petros Giannikopoulos, David N. Nguyen, Michael A. Suster, Pedram Mohseni, Umut A. Gurkan; Microfluidic capillary transit velocity as a functional measure for sickle cell disease and in vitro-derived red blood cells. Lab Chip 2026; 26 (4): 976–990. https://doi.org/10.1039/d5lc00769k
Manuscript Version
Final Publisher Version