Multispectral Imaging for Microchip Electrophoresis Enables Point-of-Care Newborn Hemoglobin Variant Screening

Introduction: Hemoglobin (Hb) disorders are among the world's most common monogenic diseases. Nearly 7% of the world's population carry Hb gene variants. Sickle cell disease (SCD) arises when hemoglobin variant mutations are inherited homozygously (HbSS) or paired with another β-globin gene mutation. Epidemiological modeling shows that universal screening could save the lives of up to 9.8 million newborns with SCD by 2050 with 85% born in sub-Saharan Africa (SSA). The World Health Organization (WHO) estimates that early diagnosis of SCD coupled with intervention programs would prevent 70% of existing SCD mortality. SCD newborn screening performed in centralized laboratories has dramatically reduced SCD mortality in resource-rich countries. SCD newborn screening requires sensitive detection of low levels of certain Hb variants (i.e., sickle Hb, HbS) in the context of high levels of expression of other Hb variants (i.e., fetal Hb, HbF). The current centralized tests used for newborn screening for SCD are high performance liquid chromatography (HPLC) and isoelectric focusing. However, in SSA and central India, where >90% of annual SCD births occur, newborn screening programs have not been implemented universally due to the cost and logistical burden of laboratory diagnostic tests. As a result, there is a need for affordable, portable, easy-to-use, accurate, point-of-care (POC) tests to facilitate decentralized hemoglobin testing in low-resource settings to enable nationwide newborn screening.