Browsing by Author "George, Alex"
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Item A Paper-Based Test for Screening Newborns for Sickle Cell Disease(Scientific Reports, 4/3/2017) Piety, Nathaniel Z.; George, Alex; Serrano, Sonia; Lanzi, Maria R.; Patel, Palka R.; Noli, Maria P.; Kahan, Silvina; Nirenberg, Damian; Camanda, João F.; Airewele, Gladstone; Shevkoplyas, Sergey S.The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings.Item A rapid paper-based test for quantifying sickle hemoglobin in blood samples from patients with sickle cell disease(American Journal of Hematology, 6/1/2016) Piety, Nathaniel Z.; Yang, Xiaoxi; Lezzar, Dalia; George, Alex; Shevkoplyas, Sergey S.Quantification of sickle hemoglobin (HbS) in patients with sickle cell disease (SCD) undergoing hydroxyurea or chronic transfusion therapy is essential to monitoring the effectiveness of these therapies. The clinical monitoring of %HbS using conventional laboratory methods is limited by high per-test costs and long turnaround times usually associated with these methods. Here we demonstrate a simple, rapid, inexpensive paper-based assay capable of quantifying %HbS in blood samples from patients with SCD. A 20 ?L droplet of whole blood and hemoglobin solubility buffer was deposited on chromatography paper. The relative color intensities of regions of the resulting blood stain, determined by automated image analysis, are used to estimate %HbS. We compared the paper-based assay with hemoglobin electrophoresis (comparison method) using blood samples from 88 subjects. The test shows high correlation (R2 = 0.86) and strong agreement (standard deviation of difference = 7 %HbS) with conventional Hb electrophoresis measurement of %HbS, and closely approximates clinically predicted change in %HbS with transfusion therapy (mean difference 2.6 %HbS, n = 4). The paper-based assay can be completed in less than 35 minutes and has a per-test cost less than $0.25. The assay is accurate across a wide range of HbS levels (10–97%) and hemoglobin concentrations (5.6–12.9 g/dL) and is unaffected by high levels of HbF (up to 80.6%). This study demonstrates the feasibility of the paper-based %HbS assay. The paper-based test could improve clinical care for SCD, particularly in resource-limited settings, by enabling more rapid and less expensive %HbS monitoring.Item Bedside Washing of Stored Red Blood Cells: A Simple Apparatus Based on Microscale Sedimentation in Normal Gravity(2015-05) Huynh, Rose Ann A.; Shevkoplyas, Sergey S.; Mohan, Chandra; George, Alex; Wu, TianfuThe aim of this study was to develop and evaluate a simple, inexpensive bedside RBC washer with the capability to process multiple pRBC units within a short period without any alteration to current blood collection and storage practices. Washing pRBC units prior to transfusion is recommended for hypersensitive patients who have a higher susceptibility towards Allergic Transfusion Reactions (ATR) due to residual plasma proteins. Unfortunately, conventional washing is bulky, expensive and laborious, due to concentrating washed units through centrifugation. In response, we developed a bedside RBC washer that utilizes gravitational sedimentation of RBCs within a saline suspension. We evaluated its ability to concentrate washed pRBC units to a therapeutic hematocrit of 65%, but it optimally concentrated to a physiological hematocrit of 41%. Concentration was found to be dependent on initial morphology of the unit. In terms of improved quality, the gravity-driven washing system performed comparably with conventional washing.Item Microfluidic and Paper-Based Devices for the Analysis of Red Blood Cells: Improving the Quality and Accessibility of Diagnosis, Monitoring and Treatment for Sickle Cell Disease(2017-05) Piety, Nathaniel Z.; Shevkoplyas, Sergey S.; George, Alex; Mohan, Chandra; Majd, Sheereen; Akay, MetinSickle cell disease (SCD) is a common inherited blood disorder which gives rise to life-long health problems. Technologies capable of sensitive and specific early diagnosis of SCD as well as accurate quantification of HbS exist, but are expensive, complex, slow, laborious, and also require stable electricity, specialized equipment, and well trained technicians. Additionally, tools for quantifying stored RBC quality and selecting well-preserved RBC units for transfusion to vulnerable patients (e.g., chronically transfused individuals with SCD) are currently lacking. These limitations have largely prevented implementation of universal newborn screening programs in low-income, developing regions (e.g., sub-Saharan Africa) and have made it difficult for clinicians to personalize care for individuals with SCD even in high-income, developed countries. In this dissertation, we engineered and validated several novel microfluidic and paper-based devices which address the limitations of existing technologies and thereby increase access to quality SCD care while enabling further understanding and optimization of transfusion medicine practices. First, we created a simple, rapid and equipment-free paper-based newborn SCD screening test capable of sensitive and specific detection of sickle hemoglobin (HbS) and SCD. Next, we made a rapid, low-cost paper-based assay for quantifying HbS in blood samples based on the color intensities of bloodstain patterns in paper, which showed high correlation and agreement with ‘gold-standard’ quantification methods. Then, we engineered a simple microfluidic device and associated image analysis algorithm capable of high throughput, automated analysis of stored RBC morphology – a potential metric for assessing the quality of stored blood and selecting well-preserved units for vulnerable patients. Finally, we used these novel devices, in combination with commercially available technologies and previously developed microfluidic devices, to quantify the impact of two novel RBC storage and rejuvenation techniques on stored RBC quality, as well as to quantify the effect of several physiologically relevant processes – i.e., RBC morphology, osmolality, aggregation and hematocrit – on overall blood rheology. If adopted, these novel tools for diagnosis, monitoring and treatment optimization could drastically increase the quality and accessibility of SCD care for millions of affected individuals worldwide, in both high-income, developed countries and resource-limited, developing regions.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 Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia(PLoS One, 1/6/2016) Piety, Nathaniel Z.; Yang, Xiaoxi; Kanter, Julie; Vignes, Seth M.; George, Alex; Shevkoplyas, Sergey S.The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age.