A Review of Electrochemical Sensors for the Detection of Glycated Hemoglobin

Abstract

Glycated hemoglobin (HbA1c) is the gold standard for measuring glucose levels in the diagnosis of diabetes due to the excellent stability and reliability of this biomarker. HbA1c is a stable glycated protein formed by the reaction of glucose with hemoglobin (Hb) in red blood cells, which reflects average glucose levels over a period of two to three months without suffering from the disturbance of the outside environment. A number of simple, high-efficiency, and sensitive electrochemical sensors have been developed for the detection of HbA1c. This review aims to highlight current methods and trends in electrochemistry for HbA1c monitoring. The target analytes of electrochemical HbA1c sensors are usually HbA1c or fructosyl valine/fructosyl valine histidine (FV/FVH, the hydrolyzed product of HbA1c). When HbA1c is the target analyte, a sensor works to selectively bind to specific HbA1c regions and then determines the concentration of HbA1c through the quantitative transformation of weak electrical signals such as current, potential, and impedance. When FV/FVH is the target analyte, a sensor is used to indirectly determine HbA1c by detecting FV/FVH when it is hydrolyzed by fructosyl amino acid oxidase (FAO), fructosyl peptide oxidase (FPOX), or a molecularly imprinted catalyst (MIC). Then, a current proportional to the concentration of HbA1c can be produced. In this paper, we review a variety of representative electrochemical HbA1c sensors developed in recent years and elaborate on their operational principles, performance, and promising future clinical applications.

Non-Enzymatic Phenylboronic Acid-Based Optode Membrane for Glucose Monitoring in Serums of Diabetic Patients and in the Culture Medium of Human Embryos

“…The sensitivity of the membrane for glucose detection was optimized using two different plasticizers (TCP and NOPE) and three ionophores (NPBA, TFPBA, and Crown-5) (see Table 1 and Figure 1 ). The hydrogen bonding and the selective interaction between the ionophore and analyte is key for developing the membrane optodes [ 31 ], especially for glucose using phenyl boronic acid as an ionophore [ 32 , 33 , 34 , 35 , 36 , 37 ]. Optode 1 fabricated with Crown-5 (ionophore 2) and TCP (plasticizer 1) exhibits a linear dynamic range of 10 −4 M to 10 −3 M, with a detection limit of 10 −4 M. Optode 2 fabricated with TFPBA (ionophore 2) exhibits a linear dynamic range of 10 −3 M to 10 −2 M, with a detection limit of 10 −3 M. Optode 3 (ionophore 3) fabricated from NPBA exhibits a broader linear dynamic range of 10 −3 M to 10 −1 M, with a detection limit of 9 × 10 −4 M. Optode 4 fabricated from NPBA (ionophore 3) but with NPOE as plasticizer exhibits a smaller linear dynamic range of 10 −2 M to 10 −1 M, with a detection limit of 1 × 10 −2 M.…”

“…Ionophores 2 and 3 are boronic acid derivatives (TFPBA and NPBA) that have different electron-withdrawing groups (three fluorides and one nitro group, respectively). These ionophores (TFPBA and NPBA) show different strengths of H-bonding with glucose [ 35 , 36 , 37 ]. The response characteristics of optodes 2 and 3 show that NPBA (ionophore 3) has a higher affinity for glucose than TFPBA (ionophore 2); see Table 1 and Figure 1 F. The TFPBA (ionophore 2) contains three fluoride groups with very high electronegativity.…”

Trends in Quantification of HbA1c Using Electrochemical and Point-of-Care Analyzers

“…Sensors comprise a sensing element that responds to the analyte and a transducer that produces the readable output. If the sensing element involves a chemical molecule, the sensor is classified as a chemical sensor, while those that employ biomolecules such as enzymes, antibodies, aptamers, oligonucleotides, etc., are classified as biosensors [ 23 ]. While chemical sensors are cost-effective and stable, they do not possess the specificity and sensitivity of biosensors [ 23 ].…”

Tungsten Disulfide Decorated Screen-Printed Electrodes for Sensing of Glycated Hemoglobin

“…Recently, different methods can be used for the detection of diabetes such as high-performance liquid chromatography (HPLC), boronate affinity chromatography, thiobarbituric acid (TBA), and ion exchange chromatography. − Although these methods are producing sensitive results, they also have various drawbacks like expensive instruments and infrastructure, smaller storage periods, and long processing time, with a complex and time-consuming sample preparation process. − Therefore, new technology and methods are needed to be introduced for removing these constraints, and a promising solution to this problem can be the use of biosensors. − Therefore, in this study, an electrochemical nanobiosensor was introduced. The biosensor is designed to identify the level of glycated hemoglobin (HbA1c) in diabetic patients.…”