Fabrication and response of alpha-hydroxybutyrate sensors for rapid assessment of cardiometabolic disease risk

Early diagnosis and treatment can prevent or delay progression of early-stage type 2 diabetes and prediabetes. Unfortunately, tests such as hemoglobin A1c (HbA1c)/fasting plasma glucose (FPG) alone fail to diagnose or miscategorize up to 40% of individuals with impaired glucose tolerance (IGT) or frank diabetes based on the rarely utilized oral glucose tolerance test (OGTT). The serum metabolite alpha-hydroxybutyrate (AHB) is increasingly recognized as a reliable IGT and diabetes predictor, and can be measured using liquid chromatography-tandem mass spectrometry. However, to address AHB adoption as a population screening tool, the reliable and low-cost measurement techniques are proposed. A periodate based oxidation was performed for an AHB-based buffer, and both nitroprusside and Raman tests confirmed the formation of a slow-oxidation product. Electrochemical tests of AHB-based buffers using electrodes such as Au-honeycomb, thiol self-assembled monolayers coated Au, 2D material (black-P) coated FTO, (3-aminophenyl) triethoxysilane modified TiO2, were performed. Many of these electrodes exhibited a systematic response when AHB concentration was varied from ~1.0-12.0 µg/ml. A colorimetric assay containing a vicinal-diol recognition moiety, additives, and a photoinitiator, exhibited a different color for AHB based buffer. Benesi-Hildebrand analysis indicated the association behavior of boronic acid and AHB. These methods have a potential to be used for rapid point-of-care measurements of AHB that could enhance population-wide diabetes and prediabetes screening strategies.