Blood Quality Diagnostic Device Detects Storage Differences Between Donors

Jani, Vivek; Mailo, Shawn Raymond; Athar, Ali; Lucas, Alfredo; Williams, Alexander T.; Cabrales, Pedro

doi:10.1109/tbcas.2017.2749304

Cited by 8 publications

(5 citation statements)

References 27 publications

(38 reference statements)

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“…RBC deformability measured using the microfluidic ratchet revealed significant inter-donor variability of freshly collected RBCs as well as inter-donor variability in RBC rigidification during storage. Interestingly, while previous efforts have reported storage-mediated mechanical deterioration of RBCs, deformability of fresh RBCs has largely been reported to be invariant 56,57 .…”

Section: Discussionmentioning

confidence: 99%

“…RBC deformability is a key part of the mechanism for splenic clearance of RBCs 50,51 , and has therefore been frequently proposed as a potential biomarker for estimating the clearance time of transfused RBCs 52,53 . Traditional methods, such as ektacytometry 28,29,54,55 , test the rheological properties of RBC derived from bulk flow, which does not correlate well with circulatory clearance time 56,57 . Microfluidic technologies present the potential to improve upon this measurement process by using microfabricated structures to approximate the deformation mechanics of the splenic microvasculature [58][59][60] .…”

Section: Discussionmentioning

confidence: 99%

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Deformability Based Sorting of Stored Red Blood Cells Reveals Donor-Dependent Aging Curves

Islamzada

Matthews

Guo

et al. 2019

Blood

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deformability Based Sorting of Stored Red Blood Cells Reveals Donor-Dependent Aging Curves

Islamzada

Matthews

Guo

et al. 2019

Blood

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“…It is well-known that RBCs undergo time dependent changes that impair deformability and various biochemical properties, namely pH, ATP, and 2,3 DPG concentration, known as storage lesion. While decay in biochemical properties is uniform across multiple populations of RBCs, our group has recently demonstrated that changes in deformability are variable and donor dependent (Jani et al, 2017a). As lipids are the most compliant of biomolecules, an increase of lipid oxidation injury and subsequent increase in membrane cell density during storage result in decreased compliance.…”

Section: Discussionmentioning

confidence: 99%

Numerical Model for the Determination of Erythrocyte Mechanical Properties and Wall Shear Stress in vivo From Intravital Microscopy

et al. 2020

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The mechanical properties and deformability of Red Blood Cells (RBCs) are important determinants of blood rheology and microvascular hemodynamics. The objective of this study is to quantify the mechanical properties and wall shear stress experienced by the RBC membrane during capillary plug flow in vivo utilizing high speed video recording from intravital microscopy, biomechanical modeling, and computational methods. Capillaries were imaged in the rat cremaster muscle pre-and post-RBC transfusion of stored RBCs for 2-weeks. RBC membrane contours were extracted utilizing image processing and parametrized. RBC parameterizations were used to determine updated deformation gradient and Lagrangian Green strain tensors for each point along the parametrization and for each frame during plug flow. The updated Lagrangian Green strain and Displacement Gradient tensors were numerically fit to the Navier-Lame equations along the parameterized boundary to determined Lame's constants. Mechanical properties and wall shear stress were determined before and transfusion, were grouped in three populations of erythrocytes: native cells (NC) or circulating cells before transfusion, and two distinct population of cells after transfusion with stored cells (SC1 and SC2). The distinction, between the heterogeneous populations of cells present after the transfusion, SC1 and SC2, was obtained through principle component analysis (PCA) of the mechanical properties along the membrane. Cells with the first two principle components within 3 standard deviations of the mean, were labeled as SC1, and those with the first two principle components greater than 3 standard deviations from the mean were labeled as SC2. The calculated shear modulus average was 1.1 ± 0.2, 0.90 ± 0.15, and 12 ± 8 MPa for NC, SC1, and SC2, respectively. The calculated young's modulus average was 3.3 ± 0.6, 2.6 ± 0.4, and 32 ± 20 MPa for NC, SC1, and SC2, respectively. o our knowledge, the methods presented here are the first estimation of the erythrocyte

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Section: Discussionmentioning

confidence: 99%

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

Islamzada

Matthews

Guo

et al. 2019

Preprint

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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

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Blood Quality Diagnostic Device Detects Storage Differences Between Donors

Cited by 8 publications

References 27 publications

Deformability Based Sorting of Stored Red Blood Cells Reveals Donor-Dependent Aging Curves

Deformability Based Sorting of Stored Red Blood Cells Reveals Donor-Dependent Aging Curves

Numerical Model for the Determination of Erythrocyte Mechanical Properties and Wall Shear Stress in vivo From Intravital Microscopy

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

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