Portable, affordable, quantitative microchip electrophoresis for hemoglobin A1C testing

PROJECT SUMMARY Diabetes is one of the most important health issues in the world. The number of people living with diabetes has quadrupled since 1980, with the greatest increase in prevalence in low and middle-income countries. Not only is diabetes a major cause of morbidity and mortality, but it can also devastate the finances of families and strain countries’ financial resources. World Health Organization is challenging governments to achieve a 25% reduction in deaths by diabetes and other non-communicable diseases by 2025. A key part of the WHO program calls for improved diagnosis and management of diabetes in primary healthcare. For many years, the hemoglobin A1C test has been used as a reliable marker for diabetes and prediabetes, since it is the best indicator of glucose control over time. Due to the relative ease of testing of A1C versus the fasting plasma glucose test, it is often the preferred option in developing countries. Current A1C tests, however, may be inaccurate due to hemoglobinopathies, and their availability has been limited. Although monitoring of A1C in diabetics improves outcomes, current testing options are: (a) expensive laboratory tests with delayed results, (b) expensive point- of-care (POC) options not suitable for remote areas, or (c) expensive and hard-to-use home monitoring kits. We have developed a POC microchip electrophoresis system that accurately identifies and quantifies hemoglobin variants, HemeChip. This system is commercialized under the product name “Gazelle™” by Hemex Health Inc. It has been extensively validated in the US, Africa, India, and South-East Asia, with a focus on sickle cell disease and beta thalassemia. Gazelle is currently selling in 13 countries with more locations planned. In the STTR Phase I project, we successfully completed two milestones by developing (1) an easy-to-use modified functional HemeChip prototype design for glycosylated hemoglobin HbA1, and (2) a quantification algorithm to detect and quantify the relative percentages of the HbA1 and non-glycosylated hemoglobin. In this STTR phase II project we plan to: (1) develop a new approach to detect the HbA1C component within the HbA1 band which incorporates the total glycosylated hemoglobin components to comply with the National Glycohemoglobin Standardization Program (NGSP) diagnostic standard, (2) fully implement the modified design of the test cartridge into the Gazelle platform and adapt the system for use at the POC by entry level healthcare workers, and (3) clinically validate the performance of the HemeChip A1C assay. Specific aims are: Aim 1: To complete the development of a test cartridge and modify the Gazelle reader to support the A1C detection and quantification. Aim 2: To demonstrate diagnostic accuracy of the HemeChip A1C test by performing a pre-certification trial according to NGSP guidelines. Aim 3: To perform clinical testing and validation in the United States and Ghana. With its ease-of-use and affordability, the proposed POC A1C test will offer a solution that meets the needs of the developing world and other underserved regions.