Abstract
Nearly 7% of the world's population live with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.
Highlights
Hemoglobin disorders are among the world’s most common monogenic diseases
The fundamental principle behind the HemeChip technology is hemoglobin electrophoresis, in which different hemoglobin variants can be separated based on electric charge differences when subjected to an electric field in the presence of a carrier substrate.[66,67]
HemeChip identified Sickle cell disease (SCD)-SS, SCD-SC, SCD Trait, Hb E Disease, and Hb E Trait with 100% accuracy (Table 2)
Summary
Hemoglobin disorders are among the world’s most common monogenic diseases. Nearly 7% of the world’s population live with hemoglobin gene variants, with the most prevalent hemoglobinopathies or structural hemoglobin variants being the recessive β-globin gene mutations, βS or S, βC or C, and βE or E.1–3 Hemoglobin S is highly prevalent in sub-Saharan Africa[4] and in tribal populations of Central India.[5]. In SCD, abnormal polymerization of deoxygenated hemoglobin S makes red blood cells (RBCs) stiff, changes membrane properties, alters shape, and triggers deleterious activation of inflammatory and endothelial cells.[12,13,14] Sickled RBCs are non-deformable and adhesive in the microcirculation,[15,16,17,18,19,20] in parts of the body where the oxygen tension is relatively low, such as the kidney or spleen.[13,17,21,22] Abnormally shaped RBCs result in microvascular occlusion and a vicious cycle of enhanced sickling, hemoglobin desaturation, and further vascular occlusion.[23,24,25] In childhood, recurrent splenic infarction from sickled RBCs increases the risk for life-threatening infections.[10,26,27,28,29] In addition, young children with SCD are at risk of life-threatening cerebral vasculopathy.[29] Afflicted patients who survive to adulthood can suffer both acute and chronic painful crises as well as cumulative organ damage and early mortality.[29,30] Infections, stroke, and numerous other SCD-related complications can be mitigated by newborn/neonatal screening and comprehensive medical care.[29,31,32] Individuals who inherit one copy of hemoglobin S and one copy of the normal hemoglobin A have sickle cell trait (Hb AS or SCD Trait). These people are healthy carriers, but have a 25% chance of transmitting SCD to their offspring
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
