# Advances and Future Perspective on Detection Technology of Human Norovirus
## 2 Detection Techniques
### Biosensor
#### 2.4.2 Optical Biosensor  
The optical biosensors for virus detection primarily include surface-enhanced Raman spectroscopy (SERS) and surface plasmon resonance (SPR). SERS has been widely used in the detection of a variety of viruses, such as hepatitis B virus, influenza virus, adenovirus, rhinovirus, human immunodeficiency virus, respiratory syncytial virus and rotavirus [114]. However, no report has been found on the application of SERS in the detection and identification of HuNoV.  
SPR biosensors have been widely applied in virus detection, such as avian influenza virus [115], Epstein-Barr virus [116], human hepatitis B virus [117] and Dengue virus [118]. [PERSON] et al. reported a quantitative SPR biosensor using feline calicivirus (FCV) as an alternative model of HuNoVs [94]. The results showed that FCV could be detected from purified cell lysates with a LOD of approximately \(10^{4}\) TCID\({}_{50}\) FCV/mL. Moreover, this biosensor had good renewability. [PERSON] et al. developed an SPR-assisted quantum dot fluorescence biosensor with a V-shaped trench. For HuNoV VLP detection, the LOD reached 0.01 ng/mL [95]. [PERSON] et al. reported an immunofluorescence nano-biosensor on the basis of localised SPR (LSPR) [96]. The linear range for detecting HuNoV VLPs was from \(10^{-14}\) to \(10^{-9}\) g/mL, and the LOD was 12.1 \(\times\)\(10^{-15}\) g/mL. For clinically isolated HuNoVs, the detection range was \(10^{2}\)-\(10^{5}\) genomic copies/mL, and the LOD was 95.0 genomic copies/mL. Furthermore, SPR can be used to analyse the binding kinetics and affinity of HuNoVs to ligands [119].  
New optical detection technologies have been developed for HuNoV detection. [PERSON] et al. developed a 3D sliding paper-based analysis device. The results could be observed directly in 10 min without additional professional equipment [97]. HuNoV GII.4 in stool samples was detected, and the LOD was 9.5 \(\times\)\(10^{4}\) genomic copies/mL. [PERSON] et al. developed an ultrasensitive SiO\({}_{2}\)-encapsulated alloyed CdZnSeS quantum dot-molecular beacon nano-biosensor for HuNoVs (Figure 5) [98]. The LODs of HuNoV RNA in human serum and buffer were 8.2 and 9.3 genomic copies/mL, respectively. [PERSON] et al. reported a smartphone-based microfluidic paper analysis device [99]. The LODs of HuNoVs in deionised water and recycled wastewater were 1 genomic copy/\(\upmu\)L and 10 genomic copies/\(\upmu\)L, respectively. [PERSON] et al. developed a colorimetric immunosensor based on graphene-gold nanoparticle (Grp-AuNPs) nanoprobes [100]. For HuNoV GII.4 VLP detection, the linear range was from 100 pg/mL to 10 \(\upmu\)g/mL. The LOD was 92.7 pg/mL, which was 112 times lower than that of traditional ELISA. The sensitivity was 41 times higher than that of commercially available diagnostic kits. [PERSON] et al. developed an ultra-sensitive sensor on the basis of a 3D total internal reflection scattering and defocusing microscope and a wavelength-dependent transmission grating to detect norovirus group-I capsid protein (NoVP). The LOD was 820 yoctomolar (yM, \(10^{-24}\) M), and the detection linear range was from 820 yM to 92.45 pM [101].  
A piezoelectric biosensor, as a newly developed mass-based biosensor, can be used in virus detection. It measures small changes in mass caused by the binding of biomolecules (such as antibodies/antigens and enzymes/substrates) [120]. QCM is the most commonly used label-free piezoelectric biosensor [121]. It has been applied to virus detection, including avian influenza viruses [122; 123; 124] and hepatitis B virus [125; 126]. Piezoelectric biosensors have ultrahigh sensitivity, and such biosensors are real-time, fast and quantifiable. However, improving their stability and anti-interference ability remains a challenge. Piezoelectric biosensors have shown potential applications, although few reports were focused on HuNoV detection using this technology.