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

Biosens Bioelectron. 2017 Mar 15;89(Pt 1):334-342. doi: 10.1016/j.bios.2016.07.019. Epub 2016 Jul 7.

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.

Keywords: 2D material; Alpha-hydroxybutyrate; Cardiometabolic disease; Electrochemical sensing; Self-assembled monolayer.

MeSH terms

  • Biomarkers / blood
  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • Boronic Acids / chemistry
  • Colorimetry / instrumentation
  • Colorimetry / methods
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Early Diagnosis
  • Electrochemical Techniques / instrumentation
  • Electrochemical Techniques / methods
  • Electrodes
  • Equipment Design
  • Gold / chemistry
  • Humans
  • Hydroxybutyrates / blood*
  • Nanostructures / chemistry
  • Nanostructures / ultrastructure
  • Phosphorus / chemistry
  • Titanium / chemistry

Substances

  • Biomarkers
  • Boronic Acids
  • Hydroxybutyrates
  • titanium dioxide
  • Phosphorus
  • Gold
  • Titanium
  • 2-hydroxybutyric acid