Glycated hemoglobin (HbA1c) has been an important biomarker for a long-term diagnosis and monitoring of diabetes mellitus. The development of a rapid, reliable, and less sophisticated device to measure HbA1c is imperative to facilitate efficient early-care diabetes management. To date, no existing aptamer-based biosensor (aptasensor) for detecting HbA1c was developed using quartz crystal microbalance (QCM). In this study, the aptamer specific to HbA1c as a novel biosensing receptor was covalently functionalized onto a QCM substrate via mixed self-assembled monolayers (SAMs). A portable QCM equipped with a liquid-flow module was used to investigate the biospecificity, sensitivity, and interaction dynamics of the aptamer functionalized surfaces. The real-time kinetic analysis of HbA1c binding to the surface-functionalized aptamers revealed the “on” and “off” binding rates of 4.19x104 M-1s-1 and 2.43x10-3 s-1, respectively. These kinetic parameters imply that the QCM-based aptasensor specifically recognizes HbA1c with the equilibrium dissociation constant as low as 57.99 nM. The linear detection of HbA1c spanned from 13 to 108 nM, with a limit of detection (LOD) of 26.29 nM. Moreover, the spiked plasma sample analysis offered compelling evidence that this aptasensor is a promising technique for developing a point-of-care device for diabetes mellitus.

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