Developing a paper-based diagnostic test for sickle cell disease

DESCRIPTION provided by applicant Sickle cell disease SCD is the most common hemoglobinopathy associated with significant life long morbidity and premature mortality Over children are born with SCD in sub Saharan Africa annually more than of them die in early childhood Most of these deaths could be prevented through simple and inexpensive prophylaxis if SCD was diagnosed soon after birth Universal screening of newborns is impractical in low income countries due to a large number of out of hospital births and the prohibitive cost of conventional testing methods A simple inexpensive sensitive and specific point of care POC device is therefore urgently needed to enable testing infants and young children during their first visit to a local clinic To address this unmet need we recently developed an ultra low cost paper based test for SCD Our test enables highly accurate diagnosis of SCD through simple visual interpretation of the pattern of the stain produced on chromatography paper by a droplet of blood mixed with hemoglobin Hb solubility buffer By running the assay in a paper substrate and using the natural color of Hb for visual discrimination we eliminated factors that interfere with conventional Hb solubility tests while gaining the capacity to accurately distinguish normal sickle trait and SCD samples ii reducing the required sample volume andlt microL iii lowering the per test cost andlt $ and iv simplifying the interpretation of results In a recent clinical study we validated our test for adlts and children andgt months old The test was able to detect the presence of sickling HbS with sensitivity and specificity demonstrating a positive predictive value of and overall diagnostic accuracy of even for patients with severe anemia Hb andlt g dL This Phase I project will focus on expanding the applicability of paper based SCD test to infants andlt months old and developing a diagnostic kit for deploying the paper based SCD test in the field We will optimize the test to increase its sensitivity for HbSandlt and investigate whether HbFandgt present in younger infants and common co morbidities such as severe anemia hyperlipidemia elevated total protein and malaria have any effect on the diagnostic accuracy of the test We will develop a sample preparation procedure utilizing low cost plastic components to enable a disposable kit determine the range of operating conditions and complete the studies required for regulatory approval of the test by the FDA A successful diagnostic kit will have the number of components number of operations and cost per test not to exceed those of existing solubility assays and be able to detect the presence of HbS in samples from infants and young children with andgt sensitivity and positive predictive value and andgt overall diagnostic value This project represents a crucial step toward the development of a low cost point of care diagnostic test for SCD that could have a potentially transformative impact on the health and well being of tens of thousands of infants and young children worldwide PUBLIC HEALTH RELEVANCE Most children born with sickle cell disease in sub Saharan Africa die in early childhood from causes that could be easily prevented through simple and inexpensive prophylaxis if their disease was diagnosed soon after birth Universal screening of newborns is impractical in low income countries due to a large number of out of hospital births and the prohibitive cost of conventional testing methods This highly innovative project plans to develop and commercialize an ultra low cost paper based diagnostic test for sickle cell disease to enable screening infants and young children during their first visit to a local clinic End of Abstract