## 2 Latest Developed Biosensors for COVID-19
### Field Effect Transistor (FET) Biosensor
#### 2.4.2 Advantages and Limitations  
Overall, the FET-based sensor provides fast detection and low LOD and does not require additional procedures for labelling during sample preparation. It is low cost, small in size and simple to operate. Nevertheless, the device sensitivity could be further improved, especially at a high concentration of sample analyte as the total number of antibodies anchored on the surface is limited by the small sensor size [109]. Non-specific interaction and screening effect could also diminish response and sensitivity [110]. To prevent non-specific binding, a blocking reagent (e.g., BSA or polyethylene glycol) is required to block the un-reacted active sites, or a covalent coupling (e.g., amide bond) is required to attach the antibody to the sensor [111; 112].  
Figure 8: Field-effect transistor biosensor for COVID-19 detection. (**A**) SWCNT-based FET biosensor. Reprinted with permission from [42]. Copyright 2020, American Chemical Society. (**B**) Graphene-based FET biosensor. Reprinted with permission from [99]. Copyright 2021, American Chemical Society. (**C**) CNT-based FET fabricated on a flexible Kapton substrate. Reprinted with permission from [100]. Copyright 2021, Elsevier Ltd. (**D**) PMO-functionalised Graphene-FET biosensor. Reprinted with permission from [106]. Copyright 2021, Elsevier B.V.  
The Debye length problem remains an entrenched obstacle [113; 114]. A layer of ions in the electrolyte above the sensor surface effectively'shields' or'screens' the analytes from the charge carriers in the semiconductor channel. The thickness of this layer is called the Debye length [111]. As shown in Figure 9A, the Debye length under physiological conditions (in 10 mM phosphate buffer saline (PBS) solution) is close to 0.7 nm [115], which is smaller than the size of antibody receptor molecules immobilised on the sensor surface, which are generally 10-15 nm in size [114]. It is difficult to detect analyte-binding that are beyond the Debye length in the physiological environment. There have been attempts to address this problem by using short antibody fragments (e.g., nanobody receptor) or aptamer (Figure 9B), which enable the analyte to bind closer to the sensor surface and achieve a detection limit down to the sub-picomolar range without the loss of selectivity [116].  
The Debye length is proportional to the reciprocal of the ionic strength. To increase the Debye length, the electrolyte ionic strength can be lowered by diluting the sample, but this, in turn, dilutes the analyte concentration and may cause a change in protein structure, resulting in the loss of protein activity and binding affinity as well. For example, in [41], the 10 mM PBS buffer was diluted to 0.01 mM, which increased the Debye length from 0.7 nm to 7 nm, comparable to the size of the positive-charged spike protein S1 subunit antibody (7-10 nm). However, dilution makes it difficult to detect low-abundance analytes [117; 118].  
Figure 9: **(A)** The Debye length increases with the reduction of buffer ionic strength. (**B**) Short antibody fragments or aptamers could be used to bring the analyte-binding closer to the sensor surface and within the Debye length.  
\begin{table}
\begin{tabular}{c c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Type of Bioemer**} & **Sensing Area \& \multirow{2}{*}{**Sensing Area \& \multirow{2}{*}{**Tangle Angle**}**} & \multirow{2}{*}{**Tangle Angle Angle**} & **Tangle Angle Angle** & **Angary Time** & \multirow{2}{*}{**Location Detection**} & **Detection** & **Detection** & **Number of Clinical** \\  & **Sensing Element** & & & & & & & &