# Current Status of HbA1c Biosensors
## 3 Analysis of Samples from Human Blood  
A good sensor system with potential for clinical use must be able to assess HbA1c level with the sensitivity and reproducibility while provide excellent operational and reagent-storage stability. The sensor system should be able to distinguish HbA1c from non-glycated hemoglobin (HbA0) or other interferences and demonstrate excellent agreement with a standard analytical method. Table 5 summarizes some the applications of biosensors in HbA1c measurement from whole-blood samples. Most of the examples described in the section above mainly focus on the method development for HbA1c determination. For practical application, HbA1c content rather than HbA1c concentration is used, which is the ratio of HbA1c concentration to total Hb concentration. Units for HbA1c content are commonly reported either in mmol/mol (used by the IFCC) or in percentage format (used by the NSGP). In general, a pretreatment of blood samples is needed to remove plasma interference followed by lysis of the RBCs. Hb and HbA1c are then measured separately using those biosensor systems. An UV-Vis spectroscopy method can be used to quantify Hb concentration before the hemolysis sample is applied to biosensors for HbA1c readout [36]. The HbA1c content can easily be calculated from these numbers. However, this kind of detection method is inconvenient in practice because the detection and separation are distinct processes. [PERSON] and coworkers have developed FcBA-based biosensors for the detection of HbA1c [25; 40]. Hbs are adsorbed to the surfactant-modified surface first, and then followed by using the mass-sensitive quartz crystal balance, and also using voltammetry to monitor total Hb and HbA1c, respectively. HbA1c binding to the APBA-modified electrodes was reversible, thereby providing a reusable sensing system. As such, [PERSON] applied the feature to develop a novel HbA1c biosensor based on flow injection [72]. They used a reticulated vitreous carbon (RVC) electrode modified with 3-APBA to separate and detect the HbA1c concentration, followed by the detection of Hb using the screen-printed electrode modified with a sol-gel film involving chitosan, and tetraethoxyl silica entrapped into carbon nanotubes. This sensor showed a good relation between signal and Hbs concentrations. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline  & **Biosensors** & \multicolumn{3}{c}{**Detection Method**} & \multicolumn{2}{c}{**Dynamic Range (ug/mL3)**} & \multicolumn{1}{c}{**Ref.**} \\ \hline
**HbA1c/HbA0** & **Electrode** & **Label/Redox Indicator** & **HbA1c/HbA0** & **HbA1c** & **HbA0** & **HbA0** \\ \hline ESMs-APBA/\(\mathrm{H}\)/\(\mathrm{p}\)-ESMs & SPCE & HCF & Impedimetric & 2.3–14\% & 5000–200,000 & [32] \\ \hline APBA-PQQ-ERGO/none & GC & PQQ & \begin{tabular}{c} Voltametric/ \\ Photometric \\ \end{tabular} & 9.4–65.8 & 92.5 & [36] \\ \hline DCCA-4-aminothiophen & Au & FcBA or anti-HbA1c Ab & \begin{tabular}{c} Voltametric/ \\ Piezoelectric \\ \end{tabular} & 0–20\% & ND & [25; 40] \\ \hline mixed SAMs wrapped & & & & & \\ nano-spheres & & & & & \\ array-anti-HbA1c/ & FET & HCF & Potentiometric & 0.05–0.1705 & 0.167–0.570 & [51] \\ anti-HbA0 Ab & & & & & \\ \hline ABPA-mercaptoethanolo & Au & ND & \begin{tabular}{c} Piezoelectric/ \\ Photometric \\ \end{tabular} & 3–11\% & 10–90 & [69] \\ \hline m-APBA agarose & & IDAs & HCF & Electrochemical & ND & ND & [70] \\ \hline APBA-column/none & GC & \
\begin{tabular}{c} Ferrocne/FC-Ab \\ \end{tabular} & Ampereometric & 4–12.6\% & 0–500 & [71] \\ \hline APBA/sol-gel film & RVC/SPE & ND & Ampereometric & 200–12,000 & 20,000–200,000 & [72] \\ \hline carboxy-EG6-undecanethiol & & & & & \\ -APBA/11-amino & Au &
\begin{tabular}{c} Luminol/\(\mathrm{H}_{2}\mathrm{O}_{2}\) \\ -1-undecanethiol \\ \end{tabular} & & & & & \\ \hline MVCNT-PTTRA-TRO & & & & & \\ \& \& & & & \\ \& \& & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 5: HbA1c biosensors for whole blood sample measurement.