DAKTARI DIAGNOSTICS, INC. — Department of Health and Human Services SBIR Phase I: NHLBI

Description

DESCRIPTION provided by applicant The World Health Organization has recently recognized sickle cell disease as a major global health concern The highest rates of sickle cell disease and sickle cell trait are seen in malaria endemic developing countries which also have the most severe resource constraints especially on clinical laboratory infrastructure Daktari Diagnostics a person venture backed start up company focused on the pressing needs for innovative global health technologies is partnering with the Whitesides laboratory at Harvard University and the University Teaching Hospital in Lusaka Zambia to develop a novel polymer system into a low cost rapid and simple to use assay for the screening and diagnosis of sickle cell disease in resource limited settings The sickle cell assay named Mpana an acronym for MultiPhase ANAlyzer and also a Swahili word meaning andquot a broad wide open channelandquot is based on self assembling polymer technology developed by the Whitesides group for industrial and medical applications and recently shown in preliminary studies in Zambia to be useful for the identification of sickle cells in blood with high sensitivity and high specificity Moreover by design these polymer systems are robust and have strong material properties that immediately suggest a path to a commercial product that can meet the difficult constraints necessary for success in resource limited settings long shelf life in environmental extremes minimal power requirements enabling battery operation simplicity of use and importantly low cost The Mpana project described here will transition the promising prototype from the academic setting into a commercial manufacturing environment For the operator the final Mpana assay will involve loading capillary blood from a heel stick or finger prick into a small microhematocrit tube pre filled with multiphase polymers that form step gradients based on density and inserting the loaded tube into a small battery operated centrifugation instrument with a simple user interface Inside the tube under centrifugation dense sickle cells settle to a specific location in the densty gradient forming a band that can be easily read visually or optically After approximately minutes the Mpana system will report out the presence of sickle cell disease sickle cell trait o a normal red blood cell profile and will differentiate HbSS from HbSC disease Results will be reported either automatically or by a visual readout and will be quality controlled through QC reagents included within the microhematocrit tube To develop the final Mpana assay we will optimize the current multi phase polymers developed by the Whiteside group for stability and manufacturability We will also develop a robust anti coagulation tube coating and final tube material that will enable easy blood collection for the operator as well as improve the sensitivit and specificity of the system through the elimination of RBC and platelet aggregation which can confound the density based assay performance In addition we will develop control microbeads of a fixed narrow density as on board QC material used to confirm the stability of the density gradient On the instrument side we will convert what has been an expensive table top centrifuge used in the preliminary Harvard studies in Zambia into a low cost portable battery operated centrifuge system a core Daktari expertise for developing simple instrumentation that has been applied previously by the Daktari engineering team to the development of a handheld battery operated CD system As a final set of preliminary studies we will evaluate the performance of the commercial prototype in the context of difficult sample specimens including specimens containing interfering substances severe anemia and a variety of hemoglobinopathies first in de identified samples obtained from the Medical University of South Carolina and finally in an initial pilot study at the University Teaching Hospital in Zambia We expect the final deliverable from this two year Phase I SBIR program will be a simple low cost instrument and assay tube capable of being used at the primary care level to rapidly and inexpensively identify children with sickle cell disease and sickle trait at a level of accuracy demonstrably matching or exceeding the expectations of the RFA PUBLIC HEALTH RELEVANCE Sickle cell disease has been transformed in the United States and developed countries due to neonatal screening and effective interventions However more than children born with sickle cell disease in Africa each year will die in infancy or earl childhood due to the painful and debilitating consequences of undiagnosed sickle cell disease infections respiratory distress and sickle cell andquot crisis andquot Most sickle cell endemic developing countries also have the most severe resource constraints Current methods to diagnose sickle cell disease which rely on complex laboratory methods cannot be used in clinics in rural Africa as a result hundreds of thousands of children are born each year with sickle cell disease go undiagnosed and do not receive effective interventions like penicillin until it is too late In ths proposal we will develop a simple rapid accurate inexpensive test for sickle cell disease the Daktari Mpana assay which can enable millions of children worldwide to be screened for sickle cell disease and to be then reached with simple and effective interventions to help them survive this difficult condition End of Abstract