RHODA: Rapid Hemoglobin-Oxygen Dissociation Assay

PROJECT SUMMARY One of the most common hemoglobin (Hb) variants is homozygous sickle hemoglobin (HbSS) which leads to sickle cell disease (SCD). Globally, an estimated 400,000 babies are born annually with SCD. Approximately 100,000 individuals are living with SCD in the United States. It is estimated that 50-90% of the babies born with SCD in Africa die by their 5th birthday, and >70% of these deaths are preventable. Effective management of SCD requires early diagnosis, which is critical in improving the quality of life. The clinical gold standard for Hb variant detection is high-performance liquid chromatography (HPLC) or point-of-care diagnostic testing, including the Gazelle Hb variant test invented at Case Western Reserve University (CWRU) and commercialized by Hemex Health, Inc. Over 400,000 Hb variant tests have been distributed by Hemex in more than 27 countries. Most current and emerging SCD therapies address symptoms by improving Hb oxygen (Hb- O2) affinity. Current laboratory and POC tests do not support treatment monitoring in SCD, especially for Hb-O2 affinity modifying therapies. The Gazelle Hb variant test has proven to be game-changing in low-resource settings for Hb variant diagnosis, but Gazelle currently doesn’t support monitoring of therapies that improve Hb-O2 affinity. A diagnostic system for Hb variant screening and Hb-O2 affinity treatment monitoring is needed. Currently, there is no FDA-approved POC diagnostic device to detect Hb variants and quantify Hb-O2 affinity in hemoglobin disorders. Gazelle Rapid Hemoglobin-Oxygen Dissociation Assay (RHODA) will be the first POC diagnostic platform for screening and treatment monitoring for SCD, integrating Hb variant diagnosis and Hb-O2 affinity functional analysis in the same platform. The proposed technology, Gazelle RHODA, is significant, innovative, and uniquely incorporates an optical spectroscopic component that enables rapid screening for Hb variants such as sickle hemoglobin (HbS). In the same test, the optical absorption spectra analysis and an integrated fluorescence measurement enable the determination of Hb-O2 affinity by measuring Hb-O2 saturation level (SO2, %) and oxygen partial pressure (pO2, mmHg), respectively determining p50. p50 is the partial pressure of oxygen at which 50% of Hb is saturated with oxygen. p50 is an important but underutilized clinical parameter due to technical and operational limitations. Rapid measurement of p50 is important for detecting genetic or disease-induced changes in blood oxygen affinity. p50 is used to determine the quality of blood/red blood cell products for chronically and critically ill patients, as well as pediatric, neonatal, post-partum, and in-utero transfusions. SO2 and pO2 measured by Gazelle RHODA are key functional and physiologic tests that help determine the oxygen-carrying capacity of the blood. This STTR Phase I project aims to: (1) Integrate RHODA into the Hemex Health Inc. Gazelle diagnostic platform for rapid, point-of-care screening of hemoglobin variants and hemoglobin-oxygen affinity; (2) Test and validate the integrated Gazelle RHODA platform in a pilot clinical study.