Browsing by Author "Torabian, Kian"
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Item A portable system for processing donated whole blood into high quality components without centrifugation(PLoS One, 1/18/2018) Gifford, Sean C.; Strachan, Briony C.; Xia, Hui; Vörös, Eszter; Torabian, Kian; Tomasino, Taylor A.; Griffin, Gary D.; Lichtiger, Benjamin; Aung, Fleur M.; Shevkoplyas, Sergey S.Background The use of centrifugation-based approaches for processing donated blood into components is routine in the industrialized world, as disparate storage conditions require the rapid separation of ‘whole blood’ into distinct red blood cell (RBC), platelet, and plasma products. However, the logistical complications and potential cellular damage associated with centrifugation/apheresis manufacturing of blood products are well documented. The objective of this study was to evaluate a proof-of-concept system for whole blood processing, which does not employ electromechanical parts, is easily portable, and can be operated immediately after donation with minimal human labor. Methods and findings In a split-unit study (n = 6), full (~500mL) units of freshly-donated whole blood were divided, with one half processed by conventional centrifugation techniques and the other with the new blood separation system. Each of these processes took 2–3 hours to complete and were performed in parallel. Blood products generated by the two approaches were compared using an extensive panel of cellular and plasma quality metrics. Comparison of nearly all RBC parameters showed no significant differences between the two approaches, although the portable system generated RBC units with a slight but statistically significant improvement in 2,3-diphosphoglyceric acid concentration (p < 0.05). More notably, several markers of platelet damage were significantly and meaningfully higher in products generated with conventional centrifugation: the increase in platelet activation (assessed via P-selectin expression in platelets before and after blood processing) was nearly 4-fold higher for platelet units produced via centrifugation, and the release of pro-inflammatory mediators (soluble CD40-ligand, thromboxane B2) was significantly higher for centrifuged platelets as well (p < 0.01). Conclusion This study demonstrated that a simple, passive system for separating donated blood into components may be a viable alternative to centrifugation—particularly for applications in remote or resource-limited settings, or for patients requiring highly functional platelet product.Item Microfluidic Device Design Informed by Red Blood Cell Morphology for Global Blood Diagnostics and Banking(2020-05) Torabian, Kian; Shevkoplyas, Sergey S.; Majd, Sheereen; Abidian, Mohammad Reza; Gifford, Howard C.; Wu, Tianfu; Sheehan, Vivien A.Just as blood diagnostic tests are ubiquitous in the clinic, blood component transfusions are among the most commonly performed medical procedures at the bedside. The many devices designed to process blood often rely on microscale flow of the complex non-Newtonian fluid. With approximately 40% of human blood comprised of red blood cells, flow dynamics are largely influenced by these relatively dense particles. Their delicate biconcave shape is essential to their deformability, aggregability, and overall viability, allowing them to bend, shear, expand, and stack as they navigate the microvasculature to deliver oxygen to surrounding tissues. As a result, shape and its many surrogates not only serve as biomarkers for their quality, but also can be exploited to improve diagnostic and blood banking devices. In this work we study red blood cells with altered morphology in various forms of sickle cell disease and in animal models with uniquely adapted vascular systems, and use our findings to develop three devices with applications in blood banking and diagnostics: a simple gravity-based device to replace industrial centrifuges that wash stored red blood cells prior to transfusion, a multi-layered microfluidic platform to separate whole blood into its component blood transfusion products, and a paper-based diagnostic device for the altered hemoglobin molecule responsible for sickle cell disease. We explore the limitations and challenges associated with current technologies used to study red blood cell deformability and aggregation, ranging from micropipettes to ektacytometers and aggregometers, with respect to balancing diagnostic robustness, methodological throughput, and access and affordability. Additionally, we take advantage of inexpensive and biomimetic microfluidic platforms to inform a design process for global health applications, considering the potential scope of these devices to improve access to some of the most widely used biomedical tools.Item Substituting Sodium Hydrosulfite with Sodium Metabisulfite Improves Long-Term Stability of a Distributable Paper-Based Test Kit for Point-of-Care Screening for Sickle Cell Anemia(Biosensors, 9/20/2017) Torabian, Kian; Lezzar, Dalia; Piety, Nathaniel Z.; George, Alex; Shevkoplyas, Sergey S.Sickle cell anemia (SCA) is a genetic blood disorder that is particularly lethal in early childhood. Universal newborn screening programs and subsequent early treatment are known to drastically reduce under-five SCA mortality. However, in resource-limited settings, cost and infrastructure constraints limit the effectiveness of laboratory-based SCA screening programs. To address this limitation our laboratory previously developed a low-cost, equipment-free, point-of-care, paper-based SCA test. Here, we improved the stability and performance of the test by replacing sodium hydrosulfite (HS), a key reducing agent in the hemoglobin solubility buffer which is not stable in aqueous solutions, with sodium metabisulfite (MS). The MS formulation of the test was compared to the HS formulation in a laboratory setting by inexperienced users (n = 3), to determine visual limit of detection (LOD), readout time, diagnostic accuracy, intra- and inter-observer agreement, and shelf life. The MS test was found to have a 10% sickle hemoglobin LOD, 21-min readout time, 97.3% sensitivity and 99.5% specificity for SCA, almost perfect intra- and inter-observer agreement, at least 24 weeks of shelf stability at room temperature, and could be packaged into a self-contained, distributable test kits comprised of off-the-shelf disposable components and food-grade reagents with a total cost of only $0.21 (USD).Item Towards bedside washing of stored red blood cells: a prototype of a simple apparatus based on microscale sedimentation in normal gravity(Vox Sanguinis, 1/1/2019) Khanal, Grishma; Huynh, R.A.; Torabian, Kian; Xia, Hui; Vörös, Eszter; Shevkoplyas, Sergey S.Background and ObjectivesInfusion of by?products of red blood cell (RBC) storage?induced degradation as well as of the residual plasma proteins and the anticoagulant?preservative solution contained in units of stored blood serve no therapeutic purpose and may be harmful to some patients. Here, we describe a prototype of a gravity?driven system for bedside washing of stored RBCs. Materials and Methods Stored RBCs were diluted to 10% haematocrit (Hct) with normal saline, matching the conventional washing procedure. The dilute RBC suspensions were passed through a column of coiled tubing to allow RBC sedimentation in normal gravity, thus separating them from the washing solution. Washed RBCs were collected using bifurcations located along the tubing. Washing efficiency was quantified by measuring Hct, morphology, deformability, free haemoglobin and total?free protein. Results The gravity?driven washing system operating at 0·5 ml/min produced washed RBCs with final Hct of 36·7 ± 3·4% (32·3–41·2%, n = 10) and waste Hct of 3·4 ± 0·7% (2·4–4·3%, n = 10), while removing 80% of free haemoglobin and 90% of total?free protein. Washing improved the ability of stored RBCs to perfuse an artificial microvascular network by 20%. The efficiency of washing performed using the gravity?driven system was not significantly different than that of conventional centrifugation. Conclusions This proof?of?concept study demonstrates the feasibility of washing stored RBCs using a simple, disposable system with efficiency comparable to that of conventional centrifugation, and thus represents a significant first step towards enabling low?cost washing of stored blood at bedside.