Detecting glycated hemoglobin in human blood samples using a transistor-based nanoelectronic aptasensor. (December 2021)

• Record Type: Journal Article
• Authors: Anand, Ankur; Chen, Chih-Yang; Chen, Tse-Hao; Liu, Yu-Cheng; Sheu, Sheh-Yi; Chen, Yit-Tsong
• Is Part Of: Nano today. Volume 41(2021)
• Publication Date: 2021-12
• Subjects: Diabetes -- HbA1c -- Aptamers -- Field-effect transistors -- Molecular docking -- Molecular dynamics simulation; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2021.101294
• Languages: English
• ISSNs: 1748-0132

Abstract

Highlights: An aptamer (AptGP ) is synthesized to target the glycated peptide (GP) of hemoglobin for diabetes diagnosis. The hairpins and groove surface of AptGP interact with the fructose and peptide moieties of GP, respectively. Binding energy (−12.3 kcal/mol) of the AptGP -GP complex indicates the high affinity of AptGP to GP or HbA1c. An AptGP -modified nanoelectronic biosensor can fast and accurately measure HbA1c levels in human blood. Graphical Abstract: ga1 Abstract: 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 β-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 AptGP ) 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-AptGP association. While the fructose group of GP binds to the hairpin region of AptGP, the peptide chain aligns with the groove surface of AptGP . This AptGP was then modified on a silicon nanowire field-effect transistor (AptGP /SiNW-FET) to recognize HbA1c in physiological solutions. To mitigate the Debye-Hückel screening effect, a porous and HbA1c-permeable polyethylene glycol (PEG) polymer was comodified on the AptGP /SiNW-FET surface (termed PEG:AptGP /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-AptGP complex determined experimentally by PEG:AptGP /SiNW-FET matches excellently with theoretical calculations. This reusable PEG:AptGP /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 point-of-care diagnostics.