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Integrated automated particle tracking microfluidic enables high-throughput cell deformability cytometry for red cell disorders
Umeå University, Faculty of Science and Technology, Department of Physics.ORCID iD: 0000-0003-1746-5157
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2019 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 94, no 2, p. 189-199Article in journal (Refereed) Published
Abstract [en]

Investigating individual red blood cells (RBCs) is critical to understanding hematologic diseases, as pathology often originates at the single-cell level. Many RBC disorders manifest in altered biophysical properties, such as deformability of RBCs. Due to limitations in current biophysical assays, there exists a need for high-throughput analysis of RBC deformability with single-cell resolution. To that end, we present a method that pairs a simple in vitro artificial microvasculature network system with an innovative MATLAB-based automated particle tracking program, allowing for high-throughput, single-cell deformability index (sDI) measurements of entire RBC populations. We apply our technology to quantify the sDI of RBCs from healthy volunteers, Sickle cell disease (SCD) patients, a transfusion-dependent beta thalassemia major patient, and in stored packed RBCs (pRBCs) that undergo storage lesion over 4 weeks. Moreover, our system can also measure cell size for each RBC, thereby enabling 2D analysis of cell deformability vs cell size with single cell resolution akin to flow cytometry. Our results demonstrate the clear existence of distinct biophysical RBC subpopulations with high interpatient variability in SCD as indicated by large magnitude skewness and kurtosis values of distribution, the "shifting" of sDI vs RBC size curves over transfusion cycles in beta thalassemia, and the appearance of low sDI RBC subpopulations within 4 days of pRBC storage. Overall, our system offers an inexpensive, convenient, and high-throughput method to gauge single RBC deformability and size for any RBC population and has the potential to aid in disease monitoring and transfusion guidelines for various RBC disorders.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019. Vol. 94, no 2, p. 189-199
National Category
Hematology
Identifiers
URN: urn:nbn:se:umu:diva-155756DOI: 10.1002/ajh.25345ISI: 000455234700015PubMedID: 30417938OAI: oai:DiVA.org:umu-155756DiVA, id: diva2:1283198
Funder
NIH (National Institute of Health), 2 P01 HL 086773-06A1R01 HL095479-06NIH (National Institute of Health), R01HL121264NIH (National Institute of Health), R21MD011590NIH (National Institute of Health), R01HL140589Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved

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Zhang, Hanqing

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