# Advances and Future Perspective on Detection Technology of Human Norovirus
## 2 Detection Techniques
### Biosensor
#### 2.4.1 Electrochemical Biosensor  
The electrochemical biosensor is a widely used biosensor [102]. Antibodies are commonly used as the biological recognition element in electrochemical biosensor. However, mAbs have high specificity and cost, whereas pAbs are relatively cheap, but they have poor specificity. Therefore, aptamers, peptides and other proteins are considered as biological recognition elements based on factors such as good stability and specificity, easy production, low cost and easy modification. The fixation of biometric components is also important. The stability and exposure of binding sites of biometric components are considered. [PERSON] et al. developed an impedance immunosensor on the basis of interdigital array microelectrodes to detect avian influenza virus H5N1 [103]. Protein A was used to fix the Fc of the antibody on the electrode and to expose the Fab. It effectively improved virus capture efficiency. [PERSON] et al. developed an electrochemical biosensor for HuNoV detection (it takes approximately 1 h) using concanavalin-A (ConA) as a biometric recognition element immobilised on a gold nanoelectrode (Figure 2) [89]. ConA had good sensitivity and selectivity, and the cost was only 2% of the cost for antibodies. This biosensor was used to detect HuNoVs in lettuce with a LOD of 60 genomic copies/mL. [PERSON] et al. developed a miniature electrochemical biosensor on the basis of aptamer modification to detect HuNoV [90]. Murine norovirus (MNV) was used as an alternative model of HuNoVs. A thiolated AG3 aptamer was modified with FAM (specific binding to MNV) and fixed on a gold electrode to capture MNV. Then, cyclic voltammetry (CV) was used to characterise the fixation of the aptamer, and square wave voltammetry was used to characterise the MNV capture. This method was simple, sensitive and fast. [PERSON] et al. reported a highly sensitive and specific electrochemical biosensor for HuNoV detection based on sulfhydryl-modified affinity peptides immobilised on a gold electrode as a bioreception element (Figure 3) [91]. The short-chain affinity peptides against the P2 domain of the recombinant VP1 (rP2) were screened as bioreception elements by a phage display technology. Then, quartz crystal microbalance (QCM), CV and electrochemical impedance spectroscopy (EIS) \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Biosensor** & **Bioreceptor** & **Signal 1** & **Target** & \begin{tabular}{c} **LOD** \\ **(with Linear Range) 2** \\ \end{tabular} & **Reference** \\ \hline \multirow{6}{*}{\
\begin{tabular}{c} Optical \\ \end{tabular} } & Molecular beacon & UV–vis & NoV GII RNA (in &
\begin{tabular}{c} In human serum: 8.2 \\ human serum) \\ \end{tabular} & \multirow{6}{*}{[98]} \\  & probes (contained 20 & absorption and & & \\  & bp complementary to & fluorescence & & \\  & NV genogroup II & emission & & \\  & RNA) & measurements & buffer) & & \\ \cline{1-1}  & Anti-norovirus & Benchtop & & \\  & protein VP1 polyclonal & fluorescence & & \\  & antibody & microscope & & \\  & & microscope & & \\ Optics & & & & \\  & Anti-norovirus & Colorimetric & & \\  & antibody (NS14) & detection & (OD\({}_{450\,\mathrm{nm}}\)) & HuNoV GII4 VLP & (100 pg/mL to 10 \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & Monoclonal capture & & & \\  & antibody (C01875M) & & & \\  & Monoclonal detection & & & \\  & antibody (C01874M) & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \hline \end{tabular} 1  
\end{table} 
Table 1: _Cont._were used for the detection of rP2 and HuNoVs GII.4. The LODs reached 99.8 nM and 7.8 genomic copies/mL, respectively. [PERSON] and [PERSON] reported a microfluidic chip integrating screen-printed carbon electrodes and polydimethylsiloxane for the electrochemical detection of HuNoVs GII.4 VLPs (Figure 4) [92]. The chip was filled with silica magnetic beads to filter clinical samples and concentrate HuNoVs.