# Current Status of HbA1c Biosensors
## 2 HbA1c Biosensors
### Indirect HbA1c Biosensors Based on the Determination of Fructosyl Valine  
HbA1c can be potentially digested to form fructosyl valine (FV) moiety, which can be measured quantitatively via an enzymatic reaction by fructosyl amino acid oxidase (FAO). There are three categories of FV-based biosensors of which applications are summarized in Table 4.  
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Type**} & **Motilied Element/Electrode/**Label or Redox Indicator** & **Detection Method** & **Dynamic Range (mM)** & **Limit of Detection (mM)** & **Applied Patient (V)** & **Reference** \\ \hline \multirow{8}{*}{Immobilized FAO} & PVA/SQ/Pt & Ampereometric & 0.2–10 & 200 & 0.6 & [54] \\ \cline{2-7}  & It NPs/Carbon & Ampereometric & 0-0.5 & ND & 0.25 & [55] \\ \cline{2-7}  & FeO\({}_{\text{Ca}}\)/NPs/Au/HCF & Ampereometric & 0.1–2 & 100 & ND & [56] \\ \cline{2-7}  & ZnO NPs-PyPy/Au/HCF & Ampereometric & 0.1–3 & 100 & ND & [57] \\ \cline{2-7}  & At Nu NPs/Cs/ & Ampereometric & 0.003–2.0 & 0.2 & 0.2 & [58] \\ \cline{2-7}  & FTO Glass Plate & Impedimeric & 0.003–2.0 & 0.2 & 0.2 & [58] \\ \hline \multirow{8}{*}{MIC} & PVA/CPE/m-PMS & Ampereometric & 0.02–0.7 & 20 & 0.1 & [59] \\ \cline{2-7}  & MIC/CPE/m-PMS & Ampereometric & 0.2–0.8 & ND & ND & [60] \\ \cline{2-7}  & MIC/Altyamine/ND/m-PMS & Ampereometric & ND & ND & 0.1 & [61] \\ \cline{2-7}  & MIC/Au/m-PMS & Ampereometric & 0.05–0.6 & ND & ND & [62] \\ \cline{2-7}  & MIP & Thermometric & 0.25–5.0 & ND & ND & [63] \\ \cline{2-7}  & None/CCPE/HTO glass & Ampereometric & 0–1.0 & ND & 1 & [64] \\ \cline{2-7}  & None/CCPE/FcBA & Ampereometric & 0.1–4.0 & 500 & 0.1 & [65] \\ \hline \hline \end{tabular}
\end{table}
Table 4: Comparison of FV sensors based on different oxidation methods.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Types**} & **Motilied Element/Electrode/**Label or Redox Indicator** & **Detection Method** & **Dynamic Range (ug/mL)** & **Reference** \\ \hline \multirow{4}{*}{Immobilized HBs} & DOCA/Au/FcBA & Voltammetric & ND & [40] \\ \cline{2-5}  & Hp/cellulose membrane or & & & \\ \cline{2-5}  & microtitler/TMB \& anti IgG-GOx & Ampereometric & 0-25\% (7.8–39 nM) & [41] \\ \hline \multirow{4}{*}{Competitive inhibition} & GPP/microtitler plate/ & & & \\ \cline{2-5}  & TMB \& anti IgG-GOx & Photometric & 1.5–10 (1 nM) & [42] \\ \cline{2-5}  & Oligophenylethylene/brane & & & \\ \cline{2-5}  & MW-FDMA-GFP/GC/FDMA & Ampereometric & 4.5–15.1\% & [43] \\ \cline{2-5}  & Au NPs-FDMA-GFP/CCE/FDMA & Ampereometric & 4.6–15.1\% & [44] \\ \cline{2-5}  & Au NPs-GPP/CCE/Ru(NH)\({}_{3}\)/\({}^{3+}\)/\({}^{2+}\) & Impedimetric & 0–23.3\% & [45] \\ \hline \multirow{8}{*}{Immobilized anti-HbA1c Antibody} & SAM 3-MPA/Au/HCF & Voltammetric & 7.5–20 & [46] \\ \cline{2-5}  & PyPy-Au NPs /Au/PPV & Potentiometric & 4–18 & [47] \\ \cline{2-5}  & SAM 1.6-hexanedithiol Au & & & \\ \cline{1-1} \cline{2-5}  & NPs/Au/HCF & Potentiometric & 4–24 & [48] \\ \cline{1-1} \cline{2-5}  & mixed SAMs/Au/HCF & Potentiometric & ND & [49] \\ \cline{1-1} \cline{2-5}  & mixed SAMs wrapped nano-spheres & Potentiometric & 0.050–0.1705 & [49; 50; 51; 52] \\ \cline{1-1} \cline{2-5}  & seed mediated growth & & & \\ \cline{1-1} \cline{2-5}  & nano-gold/Au/HCF & Potentiometric & 0.00167–0.07214 & [52] \\ \cline{1-1} \cline{2-5}  & Protein A/laser ablated Au & & & \\ \cline{1-1} \cline{2-5}  & electrode/anti HbA1c-QDs & Optic-electrochemical & ND & [53] \\ \hline \hline \end{tabular}
\end{table}
Table 3: Comparison of HbA1c immunosensors based on recognition methods.  
The first type of indirect HbA1c sensors measures the electro-oxidation of FV by FAO which is immobilized on the electrode surface prior to the enzymatic reaction (Figure 3A). The second category involves construction of a molecular-imprinted polymer (MIP) as the artificial enzyme to oxidize the FV (Figure 3B). The third type is to direct measure the oxidation of FV using electrochemical sensors (Figure 3C).