title: Fabrication and response of alpha-hydroxybutyrate sensors for rapid assessment of cardiometabolic disease risk.
abstract: 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 ~1.0-12.0µg/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.
authors.affiliation: Department of Metallurgical Engineering, University of Utah, Salt Lake City, 84112, USA. Electronic address: prashant.sarswat@utah.edu.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Sarswat
authors.affiliation: Functional Nanomatrials, Institute for Materials Science, Kiel University, Kaiserstr. 2, Kiel, D-24143, Germany.
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Mishra
authors.affiliation: Department of Metallurgical Engineering, University of Utah, Salt Lake City, 84112, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Free
mesh_terms: D015415:Biomarkers / Q000097:blood; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D001897:Boronic Acids / Q000737:chemistry; D003124:Colorimetry / Q000295:instrumentation / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D042241:Early Diagnosis; D055664:Electrochemical Techniques / Q000295:instrumentation / Q000379:methods; D004566:Electrodes; D004867:Equipment Design; D006046:Gold / Q000737:chemistry; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood*; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010758:Phosphorus / Q000737:chemistry; D014025:Titanium / Q000737:chemistry
chemical_list: D015415:Biomarkers; D001897:Boronic Acids; D006885:Hydroxybutyrates; C009495:titanium dioxide; D010758:Phosphorus; D006046:Gold; D014025:Titanium; C031570:2-hydroxybutyric acid
keywords: 2D material; Alpha-hydroxybutyrate; Cardiometabolic disease; Electrochemical sensing; Self-assembled monolayer