Colorimetric Sensing System for Monitoring Gestational Diabetes at the Point-of-Care

Abstract

Gestational diabetes is one of the most common disorders associated with pregnancy. If the blood sugar levels of the pregnant women are left unregulated during the course of a pregnancy, gestational diabetes can have several short- and long-term effects to both the pregnant woman and fetus. Using a biomarker like glycated albumin, with an intermediate measuring interval provides several advantages over standard biomarkers like glucose and HbA1c which are either too frequent or not frequent enough. Glycated albumin can efficiently monitor effects of dietary/ exercise regimen alterations without repetitive daily finger pricks or fasting. In addition, a dual assay point-of-care testing approach can provide % glycated albumin values at home with very low sample volumes, short processing times and at a more affordable cost. In this dissertation, sandwich aptamer-based assays were developed on a paper-based platform for measurement of glycated albumin. Colorimetry was used as the optical transduction technique owing to its simplicity and low cost. Since glycated albumin is measured as the ratio of the glycated version of the protein to the total protein, two separate assays have been developed. Gold nanoparticles were used as the transduction elements for colorimetric measurements since their inherent color eliminated the need for additional dyes. These system components enabled lowering of cost while maintaining important assay parameters like sensitivity and dynamic range. During the duration of this research, the ongoing COVID-19 pandemic resulted in a supply chain crisis causing an acute shortage of the target protein-glycated albumin. To overcome this issue, glycated albumin was synthesized in vitro by glycating human serum albumin protein. This in vitro glycated protein was then used and both assays were transferred to the lateral flow configuration to make the system more amenable to any point-of-care setting. A handheld colorimetric reader was incorporated into the system to make the setup more compact and portable. Finally, the assays were transferred to a dual assay cartridge and both assays were run simultaneously to obtain the value of % glycated albumin from a single cartridge.