# Current Status of HbA1c Biosensors
## 2 HbA1c Biosensors
### Affinity Biosensors Based on Boronic Acid Derivatives
#### 2.1.4 Biosensors Based on Formylphenylboronic Acid (FPBA)  
More recently, to amplify the electrochemical signal, [PERSON] and coworkers developed a competitive binding assay, also named as an enzymatic backfilling assay, in which HbA1c is immobilized on a FPBA-modified interface first, then a known amount of glucose oxidase (GOx) is backfilled on the surface. Due to the reverse concentration correlation between HbA1c and GOx, the electrochemical signal of the GOx decreases with the increasing HbA1c level [38; 39]. In their early work, poly(amidoamine) G4 dendrimer was used as the interface material to capture periodate-activated GOx, and the current of GOx decreases with increasing HbA1c level from 2.5% to 15% with a spiking method. In 2012, the cystamine-FPBA conjugate was used to functionalize a gold electrode surface in order to bind HbA1c and GOx competitively via cis-diol interaction. This method is applied for the HbA1c detection from whole blood samples. The pretreatment of Hbs via a Zn-induced precipitation with a follow-up washing-out step was carried out to remove interference of other glycoproteins or carbohydrates in whole blood. The HbA1c-GOx competitive binding assay on a cystamine-FPBA/Au electrode could measure HbA1c level in the range of 4.5-15% which covers the clinical reference range of diabetes without a need for detection labels.  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Type of** & **Modified Element/Electrode/** & \multirow{2}{*}{**Detection Method**} & \multirow{2}{*}{**Dynamic Range 1 **} & **Limit of** & \multirow{2}{*}{**Reference**} \\ \cline{4-5}
**Boronic Acid** & & & & & \\ \hline \multirow{4}{*}{FcBA} & ZrO2 NPs/PGE & \multirow{2}{*}{Amperometric} & 6.8–14\% & ND & [24] \\ \cline{2-5}  & DOCA-4-aminothiophenol & & & & \\ monolayer/Au & & 0–20\% & ND & [25] \\ \hline \multirow{4}{*}{T3 BA} & Au/HCF & Impedimetric & 0.1–1 & ND & [27] \\ \cline{2-5}  & Au/IgG-FITC & Impedimetric & 10–100 & 1 & [28] \\ \cline{2-5}  & Au/anti- HbA1c-IgG-FITC & Impedimetric & 10–100 & ND & [29] \\ \hline \multirow{4}{*}{APBA} & glutaraldehydedehyde-SAM & \multirow{2}{*}{Impedimetric} & 0.10–8.36\% & 0.024\% & [26] \\ \cline{2-5}  & Cys/IDAs/HCF & & & & \\ \cline{2-5}  & GO/GCE/HCF & Impedimetric & 10.32–61.92 & ND & [30] \\ \cline{2-5}  & glutaraldehyde dehyde-ESMs/Screen & \multirow{2}{*}{Impedimetric} & 2.3–14\% & 0.19–0.21\% & [31; 32] \\ \cline{2-5}  & printed Pt/HCF & & & & \\ \cline{2-5}  & pTTBA-Au NPs/SPE & \multirow{2}{*}{Impedimetric/ Ampometric} & 0.5–6.0\%/0.1–1.5\% & 0.052\% & [33] \\ \cline{2-5}  & PBA-ARS/GCE/HCF & \multirow{2}{*}{Potentiometric} & 5.0–50 & ND & [34] \\ \cline{2-5}  & PAPBANPs/thin & \multirow{2}{*}{Amperometric} & 63–10062 & ND & [35] \\ \cline{2-5}  & film/SPCE/PAPBA & & (0.975–156 \(\upmu\)M) & ND & [35] \\ \cline{2-5}  & PQQ-ERGO/GCE/PQQ & \multirow{2}{*}{Voltammetric} & 9.4–65.8 & 1.25 & [36] \\ \cline{2-5}  & SAM DTBA/Au & SPR & 0.43–3.49 & 0.1 & [37] \\ \hline \multirow{4}{*}{FPBA} & SAM cystamine/ & \multirow{2}{*}{Voltammetric} & 4.5–15\% & ND & [38] \\ \cline{2-5}  & Au-Si/FCM \& GOx & & & \\ \cline{1-1} \cline{2-5}  & poly(amidoamine) G4 & \multirow{2}{*}{Voltammetric} & 2.5–15\% & ND & [39] \\ \cline{1-1} \cline{2-5}  & dendrimer/Au/FCM \& GOx & & & \\ \hline \hline \end{tabular}  
* \(\upmu\)g/mL for HbA1c concentration only, % for the concentration ratio of HbA1c to HbA.  
\end{table}
Table 2: Comparison of HbA1c biosensors based on boronic acid derivatives.