SBIR-STTR Award

?Rapid, Near-Patient Tests to Monitor and Guide Therapy in Sickle Cell Disease Patients The average life expectancy of a sickle cell disease (SCD) patient is 35 years of age in the developed world (National Center for Health Statistics), and significantly younger in the third world. The disease does not have a cure, but devastating complications such as stroke, acute renal failure, and acute chest syndrome can be controlled through therapies to improve patient survival and quality of life. Hydroxyurea and red blood cell (RBC) transfusion therapies are the two most common and effective treatments for SCD. As the only FDA- approved drug for SCD, hydroxyurea increases production of erythrocytes with higher levels of fetal hemoglobin (HbF) to interfere with the polymerization of sickle hemoglobin (HbS) and reduce sickling and vaso-occlusive events. Transfusions reduce the concentration of HbS in the patient through the introduction of fully functional hemoglobin (HbA) blood. Both therapies require the monitoring of HbF or HbS levels to allow the healthcare professional to make effective clinical decisions in dosing. Currently, Hb electrophoresis or high-performance liquid chromatography (HPLC) is used to monitor levels of Hb variants in patients during SCD therapy. The tests are high-cost (often over $100/test) and require significant turnaround time (often days). Biomedomics proposes to develop low-cost, rapid tests for the quantitative measurement of HbF and HbS in SCD patients receiving hydroxyurea and/or transfusion therapy. Using a lateral flow immunoassay platform, Biomedomics proposes the development of a test that can be manufactured for a little over $1 per cartridge. The proposed test platform is rapid, small-footprint, allowing for near-patient measurements of HbF or HbS levels within 15 minutes. In addition to reducing healthcare expenses, the proposed tests allow for immediate clinical decisions at the point-of-patient treatment. Biomedomics has developed proprietary antibodies for the measurement of Hb variants by immunoassay. Utilizing these antibodies and expertise in the field of point-of-care test development, Biomedomics proposes to (1) develop quantitative tests for measurement of HbF and HbS, (2) optimize tests to meet performance criteria to test clinical samples, and (3) deploy the tests in a clinical setting. These goals will be accomplished using a lateral flow sandwich immunoassay platform in conjunction with an inexpensive sampler module to treat and apply a small volume (5 µL) of blood sample. Fifteen minutes after sample addition, the test cartridge can be analyzed in a small, point-of-care reader. The proposed tests address an important need to enable the monitoring of SCD treatments near the patient to guide therapeutic decisions.

Public Health Relevance Statement:


Public Health Relevance:
A cure does not yet exist for sickle cell disease (SCD), but diagnosis and early intervention in the thousands of affected babies born each year improves survival and quality of life-allowing patients to live into adulthood. Patients in the developed world receive treatments such as hydroxyurea to raise levels of fetal hemoglobin (HbF) and transfusion to reduce levels of sickle hemoglobin (HbS), thus lowering the risk of stroke and other complications from SCD. BioMedomics, Inc. proposes to develop and implement point-of-care tests for HbF and HbS to immediately assess, guide, and monitor therapies at the patient treatment site.

NIH Spending Category:
Bioengineering; Clinical Research; Hematology; Rare Diseases; Sickle Cell Disease

Project Terms:
acute chest syndrome; Acute Kidney Failure; Address; Adult; Adverse effects; Affect; Aftercare; Age-Years; Antibodies; Bedside Testings; Blood; Blood specimen; Blood Vessels; Buffers; Cell Therapy; Characteristics; Child; Chronic; Clinical; clinically relevant; common treatment; cost; cost effective; cross reactivity; density; detector; Development; Devices; Diagnostic; Disease; disease diagnosis; Dose; Early Intervention; effective therapy; Electrophoresis; Erythrocyte Transfusion; Erythrocytes; Event; FDA approved; Fetal Hemoglobin; Functional disorder; Goals; Guidelines; Health Professional; Healthcare; Hematological Disease; Hemoglobin; Hemolytic Anemia; High Pressure Liquid Chromatography; hydroxyurea; Hypoxemia; Immunoassay; improved; Individual; Infection; Inherited; Institutes; Knowledge; Laboratories; Lateral; Life; Life Expectancy; Measurement; Measures; Medical; meetings; Membrane; Monitor; nanoparticle; National Center for Health Statistics (U.S.); Organ; Patients; Performance; Pharmaceutical Preparations; Phase; Plastics; point of care; polymerization; Process; Production; prototype; public health relevance; Quality of life; Reader; Reagent; research study; Risk; Sampling; screening; Series; Sickle Cell; Sickle Cell Anemia; Sickle Hemoglobin; sickling; South Carolina; Specificity; stroke; System; Techniques; Testing; Therapeutic; Time; TimeLine; Tissues; tool; Transfusion; treatment site; Universities; Variant

SCD or sickle-cell anemia (SCA) is a hereditary blood disorder characterized by loss of flexibility of red blood cells and resulting in mortality and other serious complications. The greatest burden of SCD is in sub-Saharan Africa, where 75% of the 300,000 annual global births of affected children occur. Estimates are that 50-80% of these affected children will die before reaching adulthood despite the availability of low cost, effective therapies. SCD can be diagnosed (and subsequently treated) through newborn screening programs HPLC or electrophoresis systems, but these tools are too expensive and generally unavailable in low resource environments. The World Health Organization (WHO) estimates that 70% of SCD deaths in sub-Saharan Africa are preventable and has declared SCD a Public Health Priority. Field studies need to be performed with a significant sample size for significant calculation. Sickle cell disorders are present in the US, but far more prevalent in Africa, India, and the Middle East. Additionally, the test is designed for use in low-resource environments, including rural clinics as well as US CLIA-waived sites. Field studies in clinical sites found in sub-Saharan Africa are an ideal setting to stress test the product in a low-resource environment targeting a population with the highest prevalence of disease. Our study centers will include African sites in Nigeria, Ghana, Angola, Tanzania, and Kenya but also include US sites in South Carolina. The international sites include the Aminu Kano Teaching Hospital, Hasiya Bayero Pediatric Hospital, Murtala Mohammed Specialist Hospital, and University of Abuja Teaching Hospital amongst others. US sites include the COBRA Human Services Agency, Orangeburg Area Sickle Cell Foundation, James R. Clark Memorial Sickle Cell Foundation, the Louvenia Barksdale Sickle Cell Anemia Foundation, and the Medical University of South Carolina. These sites will have facilities and staffing to conduct sampling and testing of the Sickle SCAN® product. The sites will have access to established method testing, coordinated by the clinical consultant. Any compensation to foreign sites will not be drawn from SBIR funding.

Public Health Relevance Statement:
Project Narrative Diagnosis and early intervention of the 300,000 babies born with sickle cell disease each year can dramatically improve survival and mortality—allowing patients to live into adulthood. BioMedomics is developing a point-of- care, multiplexed lateral flow immunoassay to detect hemoglobins A, S, and C in adults, children, and newborns. The Sickle SCAN® test is a simple, low-cost device for the rapid identification of sickle cell disease and trait in low-resource environments such as a rural clinic in Africa, a local pharmacy in India, or a community screening fair in the US.

NIH Spending Category:
Bioengineering; Biotechnology; Clinical Research; Health Services; Hematology; Pediatric; Prevention; Rare Diseases; Sickle Cell Disease

Project Terms:
5 year old; Accounting; Address; Adult; Affect; Africa; Africa South of the Sahara; African; African American; Angola; Antibiotics; Antibodies; Area; assay development; base; Bedside Testings; Birth; Blood specimen; Buffers; Cessation of life; Child; Clinic; Clinical; clinical research site; Clinical Trials; Communities; Contracts; cost; cost effective; Country; cross reactivity; design; Detection; detector; Development; Devices; Diagnosis; Disease; disease diagnosis; Early Intervention; Electricity; Electrophoresis; Environment; Equipment; Erythrocytes; Evaluation; Family Planning; Feedback; field study; Financial compensation; flexibility; Foundations; Funding; Ghana; Goals; Guidelines; Health Personnel; Hematological Disease; Hemoglobin A; Hemoglobin C; High Pressure Liquid Chromatography; High Prevalence; Housing; Human; Immunoassay; improved; India; Infection; Inherited; Institutes; International; Kenya; Laboratories; Lateral; Life; manufacturing process; Medical; meetings; Membrane; Methods; Middle East; Monoclonal Antibodies; mortality; nanoparticle; Neonatal Mortality; Neonatal Screening; Newborn Infant; Nigeria; Patients; Pediatric Hospitals; Performance; Pharmacy facility; Phase; Physicians' Offices; point of care; polyclonal antibody; Population; Preventive care; Printing; Process; Production; programs; prophylactic; public health priorities; Quality Control; Resources; Rural; Sample Size; Sampling; scale up; screening; Sensitivity and Specificity; Services; Sickle Cell; Sickle Cell Anemia; Sickle Cell Trait; Sickle Hemoglobin; sickling; Site; Small Business Innovation Research Grant; South Carolina; Specialist; Stress Tests; Suggestion; System; Tanzania; Teaching Hospitals; Techniques; Testing; Time; TimeLine; tool; Trademark; trait; Uganda; United States; Universities; University Hospitals; Validation; World Health Organization