Affinity sensor for haemoglobin A1c based on single-walled carbon nanotube field-effect transistor and fructosyl amino acid binding protein

Abstract

Haemoglobin A1c (HbA1c) is a significant glycaemic marker for diabetes mellitus. The level of HbA1c reflects the mean blood glucose level over the prior 2-3 months and it is useful for the assessment of therapeutic effectiveness and for diagnosis. In this study, we report the label-free affinity sensor for HbA1c based on the chemiresistor-type field-effect transistor, which has a simple sensor configuration. Single-walled carbon nanotubes (SWNTs) were used as the transducing element. The fructosyl amino acid binding protein from Rhizobium radiobacter (SocA), which binds to α-fructosyl amino acid specifically, was used as the biorecognition element for fructosyl valine (FV), the product of the proteolytic hydrolysis of HbA1c. The developed sensor shows the ability to measure as low as 1.2 nM FV, which is 14-fold more sensitive compared to the previously reported fluorescence-based sensor using SocA. This sensor also exhibits high specificity where no significant response is observed from either fructosyl lysine (FK) or glucose, which are potential interferents. FK is the ε-fructosyl amino acid from glycated albumin, another glycated protein, whereas glucose is naturally present at very high concentration in the blood. We propose that the modulation of the surface charges on the SWNTs caused by the conformational change in SocA upon ligand binding leads to the proportionate changes in the number of carriers in the SWNT channel.

Keywords: Field-effect transistor; Fructosyl amino acid binding protein; Fructosyl valine; Haemoglobin A1c; Single-walled carbon nanotube; SocA.