SBIR-STTR Award

Sickle cell disease (SCD) is an inherited anemia in which formation of hemoglobin polymer causes destruction of the red blood cells, a process called hemolysis. SCD is recognized as a significant global public health problem. Over 90% of the 300,000 annual births with SCD occur in resource-poor countries, and most of the affected children die from preventable causes. Thus, there exists an urgent need for technologies to screen infants for SCD so that appropriate health care measures can be initiated. The aim of this proposal is to develop a robust point-of-care diagnostic system based upon measurement of breath carbon monoxide (CO) level. CO in exhaled breath is largely derived from the oxygen-dependent catabolism of heme during destruction of red blood cells, a process accelerated in SCD. Capnia has a device, CoSense", which is currently cleared by the FDA for End-Tidal Carbon Monoxide (ETCO) monitoring. The use of end-tidal breath samples allows the measurement of exhaled CO in young children who cannot provide a forced breath sample. A recent preliminary study demonstrated that ETCO levels measured by CoSense were 6-fold higher in SCD than the controls. Therefore, CoSense, as a screening tool, may be extremely helpful in identifying infants with SCD in resource-poor countries where newborn screening is not available. In Phase I of the SBIR proposal, the current device will be modified to extend its temperature operating range.

Public Health Relevance Statement:


Public Health Relevance:
Over 300,000 babies are born with sickle cell disease every year, principally in Africa and India. Most of these children die in the first few years of life uness the disease can be diagnosed early. In this project, we propose to develop a device which measures carbon monoxide concentration in the breath to screen for sickle cell disease during infancy. (End of Abstract)

Project Terms:
abstracting; Accounting; Adult; Affect; Africa; Algorithms; Anemia; Antibiotics; arm; base; Birth; Blood specimen; Blood Tests; Cannulas; Carbon Monoxide; Caring; Catabolism; Child; commercial application; cost; Country; design; Detection; Developing Countries; Devices; Diagnosis; Diagnostic tests; Disease; disorder control; Early Diagnosis; Enrollment; Environment; Erythrocytes; Exhalation; Financial compensation; Gases; General Practices; Health education; Healthcare; Heme; hemoglobin polymer; Hemolysis; Hemolytic Anemia; High Prevalence; High temperature of physical object; Home environment; Hospitals; Human Resources; Humidity; Hydrogen; improved; India; infancy; Infant; Inherited; innovation; Laboratories; Life; Live Birth; Measurement; Measures; Medical; Modeling; Modification; Monitor; Mortality Vital Statistics; Neonatal Screening; Newborn Infant; Nose; Output; Oxygen; Pediatric Hospitals; Performance; Phase; point of care; point-of-care diagnostics; Populations at Risk; Porphyrins; Power Sources; Primary Health Care; Process; programs; prophylactic; public health medicine (field); public health relevance; Research; Research Infrastructure; Resources; Sampling; screening; sensor; Sickle Cell Anemia; Signal Transduction; Small Business Innovation Research Grant; Solutions; Staging; System; Techniques; technological innovation; Technology; Temperature; Testing; tool; Training; United States; Vaccination; Western Africa

More than 300,000 babies are born annually with sickle cell disease (SCD), 90% of which occur in developing countries, with the largest number in Nigeria. A majority of children with SCD die before 5 years, but when early SCD screening is coupled with health care management, mortality can be reduced dramatically. Unfortunately, because universal screening requires blood samples from infants, it is rarely done in resource-limited settings where it is expensive and hard to implement. A simple, economical and portable point-of-care (POC) screening test that is well accepted by families, avoids the need for blood sampling, and is easily integrated into the existing community health care system without diverting time and resources from other healthcare priorities is critically needed. To this end, Capnia has modified the portable CoSense End Tidal Carbon Monoxide (ETCO) Monitor to make it suitable for point of care use as a SCD screening tool in tropical climates. The monitor non-invasively measures carbon monoxide in breath, a byproduct of hemolysis, and clearly distinguishes between children with or without SCD. Because measurements can be made without a forced breath sample, it is suitable for use in infants and young children who cannot reliably follow sample collection commands. Further, the only disposable item required is an inexpensive nasal cannula. Thus, this simple-to-use device meets all of the desirable characteristics for use as a SCD screening tool in low resource settings. In order to fully prepare the device and develop an SCD screening regimen for commercial deployment we propose four aims. In Aim 1 we will determine the optimal age at which infants should be screened using ETCO and a recommended ETCO threshold at which they should be referred for further SCD. We will also define the sensitivity and specificity of detecting SCD in Nigerian children. In Aim 2 we will enhance the usability of CoSense-S to make it suitable for field use in Nigeria and develop training materials to support its commercial deployment for SCD screening. Work in Aim 3 will test the reliability and ease of use of CoSense-S in field conditions in Nigeria. Our goal is to test and validate the modified monitor, CoSense-S, for SCD screening in the field in Nigeria. If successful, we will be ready to commercialize a device that will for the first time make widespread screening for SCD feasible in low resource settings.

Public Health Relevance Statement:
PROJECT NARRATIVE A vast majority of the more than 300,000 children born annually with sickle cell disease in developing countries die from a lack of early diagnosis, significantly contributing to the under-5 mortality rate. Our goal is to test and validate a novel device, CoSense-S, which employs inexpensive, non-invasive breath testing to screen for sickle cell disease. If successful, we will be ready to commercialize a device that will for the first time make widespread screening for sickle cell disease feasible in low resource settings.

Project Terms:
Adoption; Affect; Age; base; Blood specimen; Blood Tests; Breath Tests; Cannulas; Carbon Monoxide; care systems; Characteristics; Child; Clinical; Clinical Trials; Community Healthcare; Comorbidity; Coupled; Cross-Sectional Studies; Data; Day center care; design; Developing Countries; Devices; Disease; Early Diagnosis; Electrophoresis; Ensure; Family; Fetal Hemoglobin; field study; Focus Groups; G6PD gene; Genetic; Goals; graphical user interface; Guidelines; Health Personnel; Healthcare; Hemoglobin; Hemolysis; improved; Industry; Infant; Instruction; Laboratories; Language; Malaria; Measurement; Measures; Medical Device; Minor; Modification; Monitor; mortality; Neonatal; neonate; Nigeria; Nigerian; Nose; novel; Performance; point of care; portability; Protein Isoforms; Protocols documentation; Random Allocation; Reading; Regimen; Resources; sample collection; Sampling; screening; Sensitivity and Specificity; Sickle Cell Anemia; Sickle Hemoglobin; skills; Testing; Time; tool; Training; Tropical Climate; usability; Work