SBIR-STTR Award

Hemoglobin (Hb) disorders are among the world's most common monogenic diseases. Nearly 7% of theworld's population carry Hb gene variants. Sickle cell disease (SCD) arises when Hb mutations are inheritedhomozygously (HbSS) or paired with another β-globin gene mutation. Globally, an estimated 400,000 babiesare born annually with SCD, and 70%-75% are in sub-Saharan Africa (SSA). It is estimated that 50-90% inSSA die by their 5th birthday, 70% of these deaths are preventable. Effective management of SCD involvesearly diagnosis, and genetic counselling, and, importantly, nationwide newborn screening (NBS). NBSprograms utilizing centralized laboratories have dramatically reduced SCD mortality in high-resource countries.NBS requires sensitive detection of relatively low levels of Hb variants in the presence of high fetal Hb (HbF).Normal HbA and sickle HbS should be accurately identified in the presence of high levels (up to 90%) of HbF.The current gold standard for Hb variant testing is high-performance liquid chromatography (HPLC), whichrequires expensive equipment and reagents, highly trained personnel, and modern laboratories. In low-resource regions, very few centralized laboratories can perform costly Hb testing. Testing is not available to thelarge percentage of infants born outside of a major hospital or city. There is an unmet need for affordable,portable, easy-to-use, accurate, point-of-care (POC) tests to facilitate decentralized Hb testing to enablenationwide NBS programs. In 2019, the World Health Organization (WHO) listed Hb electrophoresis as anessential in vitro diagnostic in low- and middle-income countries. We have developed a POC microchipelectrophoresis Hb variant testing system, MicroChip Electrophoresis (MCE), under the product name "GazelleHb Variant" by Hemex Health, Inc. MCE reports Hb phenotype, Hb quantification (%Hb), and an interpretivestatement showing genotype (such as SCD, Sickle Cell Trait, or Normal). MCE has been extensively validatedfor hemoglobinopathies, including SCD, hemoglobin E disease, and thalassemia. Newborns and infants below6 weeks of age have very low concentrations of Hb variants other than Hb F which is high, therefore animprovement to lower the limit of detection (LoD) is needed to support NBS programs worldwide. Bydecreasing the LoD from the current 10% to 2%, newborns and infants can be screened with this affordablesystem. The innovation in this SBIR Phase I is the integration of multi-spectral imaging and machine learning baseddata analysis capability to MCE to develop MCE+ to accurately screen newborns for common Hb variants. Wepropose the following aims: Aim 1: Integrate multi-spectral imaging and machine learning algorithm into theMCE platform to enable identification and quantification of hemoglobin variants in newborns. Aim 2: Performclinical testing of the MCE+ multi-spectral newborn screening system. Significance of this project is that MCE+ isthe only affordable POC system for quantitative and objective hemoglobin variant testing that allows screening atbirth.

Public Health Relevance Statement:
PROJECT NARRATIVE Up to 50 to 90% of children born with sickle cell disease (SCD) in economically disadvantaged countries (over 400,000 per year) die before the age of five, although the WHO estimates that 70% could be saved through simple, cost-effective treatments. Early diagnosis starting at birth is critical for implementing effective disease management, but newborn screening is a challenge for low resource environments where a decentralized, point-of-care solution is needed. This project enables our affordable, point-of-care platform based on microchip electrophoresis technology to accurately perform newborn screening.

Project Terms:
Africa ; Africa South of the Sahara ; Sub-Saharan Africa ; Subsaharan Africa ; Age ; ages ; Sickle Cell Anemia ; Hb SS disease ; HbSS disease ; Hemoglobin S Disease ; Hemoglobin sickle cell disease ; Hemoglobin sickle cell disorder ; sickle cell disease ; sickle cell disorder ; sickle disease ; sicklemia ; Southeastern Asia ; Southeast Asia ; beta Globin ; B-globin ; β-globin ; Birth ; Parturition ; Blood ; Blood Reticuloendothelial System ; Child ; 0-11 years old ; Child Youth ; Children (0-21) ; youngster ; High Pressure Liquid Chromatography ; HPLC ; High Performance Liquid Chromatography ; High Speed Liquid Chromatography ; Cities ; Clinical Research ; Clinical Study ; Data Analyses ; Data Analysis ; data interpretation ; Decentralization ; Disease ; Disorder ; Electrophoresis ; Electrophoretic Fractionation ; Environment ; Equipment ; Fetal Hemoglobin ; Fetal Hb ; HbF ; Hemoglobin F ; fetal form of hemoglobin ; fetal globin ; Genetic Counseling ; Genotype ; Ghana ; Gold Coast ; Gold ; Health ; Health Status ; Level of Health ; Hemoglobin concentration result ; hemoglobin level ; Hemoglobinopathies ; Hemoglobin ; Hospitals ; Teaching Hospitals ; India ; Infant ; Newborn Infant ; 0-4 weeks old ; Newborns ; newborn child ; newborn children ; Laboratories ; Modernization ; mortality ; Mutation ; Genetic Alteration ; Genetic Change ; Genetic defect ; genome mutation ; Names ; Neonatal Screening ; Newborn Infant Screening ; newborn screening ; Phenotype ; Race ; Racial Group ; Racial Stocks ; Reagent ; Reference Standards ; Resources ; Research Resources ; Sickle Cell Trait ; HbAS ; Specificity ; Technology ; Testing ; Thalassemia ; Work ; World Health Organization ; Gender ; Caring ; base ; improved ; Clinical ; Phase ; Variant ; Variation ; Ensure ; Training ; Hemoglobin E Disease ; Point of Care Technology ; Point-of-Care Systems ; machine learned ; Machine Learning ; Disorder Management ; Disease Management ; Hereditary ; Inherited ; System ; Country ; innovative technologies ; early detection ; Early Diagnosis ; Gene Alteration ; Gene Mutation ; Accuracy of Diagnosis ; diagnostic accuracy ; trait ; novel ; Economically Deprived ; economic disadvantage ; economically disadvantaged ; underclass ; Economically Deprived Population ; Manpower ; personnel ; Human Resources ; Reporting ; miniaturize ; portability ; Drops ; Microchip Electrophoresis ; Detection ; research clinical testing ; Clinical Evaluation ; Clinical Testing ; clinical test ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Validation ; Development ; developmental ; point of care ; cost ; genetic variant ; Gene variant ; allele variant ; allelic variant ; genomic variant ; sickling ; Population ; innovation ; innovate ; innovative ; commercialization ; screening ; Mendelian disorder ; Mendelian disease ; Mendelian genetic disorder ; monogenic disease ; monogenic disorder ; single-gene disease ; single-gene disorder ; spectrograph ; spectral image ; spectral imagery ; spectrum image ; spectrum imagery ; low and middle-income countries ; LMIC ; screening program ; preventable death ; preventable mortality ; machine learning algorithm ; machine learned algorithm ; in-vitro diagnostics ; detection limit ; cost effective treatment ; cost effective therapy ; point of care testing ;