Detecting glycated hemoglobin in human blood samples using a transistor-based nanoelectronic aptasensor

Glycated hemoglobin A1c (HbA1c) is a measure of long-term glycemic control in chronic diabetes-related complications. In this study, the glycated N-terminus of the hemoglobin beta-chain, i.e., the glycated peptide (GP) of Fru-Val-His-Leu-Thr-Pro-Glu-COOH, was used as a template to isolate a novel aptamer (denoted by Apt(Gp)) via the systematic evolution of ligands by the exponential enrichment (SELEX) technique. Molecular docking/simulation studies revealed that both H-bonding and nonbonded interactions dominate the GP-Apt(Gp) association. While the fructose group of GP binds to the hairpin region of Apt(Gp), the peptide chain aligns with the groove surface of Apt(Gp). This Apt(Gp) was then modified on a silicon nanowire field-effect transistor (Apt(Gp)/SiNW-FET) to recognize HbA1c in physiological solutions. To mitigate the Debye-Hiickel screening effect, a porous and HbA1c-permeable polyethylene glycol (PEG) polymer was comodified on the Apt(Gp)/SiNW-FET surface (termed PEG:Apt(Gp)/SiNW-FET) to enable the detection of HbA1c in peripheral human blood. The binding free energy (-12.30 +/- 0.05 kcal/mol) of the GP-Apt(Gp) complex determined experimentally by PEG:Apt(Gp)/SiNW-FET matches excellently with theoretical calculations. This reusable PEG:Apt(Gp)/SiNW-FET aptasensor detects HbA1c levels in human blood as accurately as conventional capillary electrophoresis but has the advantages of being fast and cost-effective and thus is amenable to pointof-care diagnostics. (C) 2021 Elsevier Ltd. All rights reserved.