A fundamental challenge in the transfusion of red blood cells (RBCs) is that not all donated RBC units will confer the same benefit to the recipient. While some RBC units will remain in circulation for long periods after transfusion maintaining homeostasis, some will be cleared rapidly, leading to the need of an increased number of transfusions. This variability stems, in part, 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. Previous methods for characterizing RBC deformability have been limited in their sensitivity and consistency. As a result, these methods have only been able to characterize pathological and chemically degraded RBCs, but have not been able to distinguish differences between healthy donors.
Recently, we developed a microfluidic device to sort RBCs based on deformability using a matrix of asymmetrical tapered constrictions that form microfluidic ratchets. Due to the geometric asymmetry of the taper, the force required to deform cells through the constriction along the direction of taper is less than against the direction of taper. Coupling this deformation asymmetry with an oscillatory flow creates a ratcheting effect that selectively transports cells based on their ability to squeeze through each microscopic constriction. Importantly, this oscillatory flow also minimizes the contact between cells and the filter microstructure to prevent clogging and fouling to ensure that a consistent filtration force is applied to each cell.
We measured the deformability profiles of eight healthy donors using the microfluidic ratchet device. We found the deformability profile to be consistent for each donor over multiple donations. We also found significant variability across different donors. We then cold stored donated RBCs in SAGM media in plastic test tubes for 14 days to accelerate cold storage related damage. We find that the aging curve of RBC deformability varies significantly across donors, but is also consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of accelerated aging.
This study illustrates a potential route to identify high-quality donors, or super-donors, that can provide RBCs that maintain their integrity during cold storage. Being able to identify these donors will enable blood bankers to reserve high-quality RBC units for chronic transfusion recipients, which will reduce the total number of transfusions for these patients and increase the overall blood supply.
Disclosures
Ma: Patent (US 9880084): Other: Inventor.
Deformability based sorting of stored red blood cells reveals donor-dependent aging curves
