Deformability based sorting of stored red blood cells reveals donor-dependent aging curves

Abstract

A fundamental challenge in the transfusion of red blood cells (RBCs) is that a subset of donated RBC units may not provide optimal benefit to transfusion recipients. This variability stems from the inherent ability of donor RBCs to withstand the physical and chemical insults of cold storage, which ultimately dictate their survival in circulation. The loss of RBC deformability during cold storage is well-established and has been identified as a potential biomarker for the quality of donated RBCs. While RBC deformability has traditionally been indirectly inferred from rheological characteristics of the bulk suspension, there has been considerable interest in directly measuring the deformation of RBCs. Microfluidic technologies have enabled single cell measurement of RBC deformation but have not been able to consistently distinguish differences between RBCs between healthy donors. Using the microfluidic ratchet mechanism, we developed a method to sensitively and consistently analyze RBC deformability. We found that the aging curve of RBC deformability varies significantly across donors, but is consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of cold storage in standard test tubes. The ability to distinguish between RBC units with different storage potential could provide a valuable opportunity to identify donors capable of providing RBCs that maintain their integrity, in order to reserve these units for sensitive transfusion recipients.Donor-dependent Red Cell Aging

Blood Unit Segments Accurately Represent the Biophysical Properties of Red Blood Cells in Blood Bags but Not Hemolysis

“…The copyright holder for this preprint (which this version posted July 21, 2021. ; https://doi.org/10.1101/2021.07.20.453156 doi: bioRxiv preprint with an increased frequency of post-surgery mortality, following transfusion of blood stored more than two weeks 31 . Importantly, however, we and others have reported that RBC deformability loss is donor dependent, where some donors are able to provide highly stable RBCs while other donors provide rapidly degrading RBCs 2,3,[32][33][34] .…”

“…The microfluidic ratchet device was manufactured as previously described 34,36,37 using photolithographic microfabrication and replica molding of Polydimethylsiloxane (PDMS, Sylgard-184, Ellsworth Adhesives). To measure RBC deformability, the device is first primed by filling with HBSS+0.2% Pluronic buffer for 15 minutes until fully buffered.…”

“…The microfluidic ratchet device sorts RBCs based on their ability to deform through a constriction matrix of different sizes into 12 distinct outlets 34,36,37 . The RBCs are flowed through the device using an oscillatory (upward/downward) sorting pressure and constant forward pressure system, which moves the sample forward, through the sorting matrix.…”

Relation between Exercise Performance and Blood Storage Condition and Storage Time in Autologous Blood Doping

“…However, some aspects will be described herein. RBC lose their deformability, an important parameter to ensure nutrient and oxygen supply in the microcirculation, during CS [ 82 ], while RBC deformability of cryopreserved RBC appears not to be negatively affected [ 36 ]. The decrease in RBC deformability in CS might be associated to RBC senescence, which includes not only a reduction in cell volume, externalization of phosphatidylserine, and reduction in CD47 [ 83 ], but also a loss in 2,-3-DPG and ATP and reduction in nitric oxide bioavailability.…”

Assessment of transient changes in oxygen diffusion of single red blood cells using a microfluidic analytical platform

“…In contrast, the increase of D50 in stored RBCs suggests the apparent benefit of faster O 2 supply to the tissues. RBC storage has been shown to increase the MCV of RBCs in some studies 53 – 58 , albeit marginally (<5%) especially when stored at 4 °C. Yet other studies showed no appreciable changes with storage 59 – 61 .…”