Development of a colorimetric paper fluidic dipstick assay for measurement of glycated albumin to monitor gestational diabetes at the point-of-care

Gestational diabetes mellitus (GDM) affects between 2 and 14% of pregnant women in the United States every year. Currently, glucose and hemoglobin A1c (HbA1c) are the standard biomarkers used to monitor GDM but HbA1c is representative of 2–3 months of glycemic data and is too infrequent for managing clinical impact of GDM while glucose provides multiple daily readings which arguably are not entirely necessary for mild to moderate GDM and often result in non-compliance from the patient's side. Thus, there is a need for an intermediate biomarker which can be used effectively to monitor the glycemic status of GDM patients. Serum albumin, the most abundant protein in blood, undergoes non-enzymatic glycation in the bloodstream. Owing to its half-life of ~21 days, it can effectively be used as an intermediate biomarker. Normal level of glycation of albumin is between 10 and 16% whereas in diabetic patients it is much higher, between 16 and 40%. Thus, a point-of-care (POC) monitoring system to detect glycated albumin (GA) as a % of total serum albumin has been developed here. Specifically, a dipstick paper fluidic test to measure % glycated albumin has been developed that used an aptamer assay with gold nanoparticles to produce colorimetric measurements. Both the glycated and unglycated versions of albumin were measured in their relevant physiological concentration ranges – 50 μM–300 μM with a limit of detection (LoD) of 6.5 μM for glycated albumin and 500 μM–750 μM with a LoD of 21 μM for unglycated serum albumin. The use of aptamers as recognition elements, instead of commonly used antibodies, not only provided the required sensitivity, specificity, and dynamic range but they also have the added advantage of being stable at room temperature for an extended period of time providing the potential for these dipstick tests to be used for GDM monitoring at the point-of-care (POC).