## 2 Latest Developed Biosensors for COVID-19
### Electrochemical Biosensor
#### 2.3.1 Electrochemical Biosensor for COVID-19  
Rural communities bear a higher burden from the COVID-19 outbreak due to limited healthcare resources. The RT-PCR diagnostic method is costly and complicated in procedures, which makes it unsuitable for the low-resource area. Disposable electrochemical biosensors based on SPEs are promising alternatives for rapid, affordable, direct detection of SARS-CoV-2 at the point of care. Figure 4: Screen-printed-electrode based electrochemical biosensor. Typical interactions on the working electrode among the biorecognition element, target analyte and detection antibody labelled with an enzyme. As shown, the enzyme oxidises an enzymatic substrate to produce an electroactive product that releases electrons, which are transduced as a measurable electrochemical signal. Figure 5A shows a recent graphene-based SPE sensor, which is functionalised with a monoclonal anti-spike antibody for detecting SARS-CoV-2 spike antigen. The sensor detected spike protein in a saliva sample, by using square wave voltammetry (SWV) to measure the change of the ferri/ferrocyanide signal, in about 45 min. The ferri/ferrocyanide couple was used as a redox probe and the electrochemical detection was achieved by measuring the peak current of the ferro/ferricyanide redox after the biomolecular binding event on the sensing surface. The peak current is reduced because the target analyte prevented the redox probe from contacting the conductive surface [82]. The LOD of this sensor for spike protein was 20 ug mL\({}^{-1}\). However, its sensitivity is lower compared to laboratory ELISA tests, which can detect as low as 3 ng mL\({}^{-1}\)[39]. In another approach, magnetic beads (MBs)-based immunoassay is coupled with electrochemical detection for viral RNA and antigen detection with high sensitivity. MBs have the potential to reduce the incubation time from hours to minutes and is easily separated from a complex matrix under the action of an external magnetic field; therefore non-specific adsorption is almost negligible [83; 84]. [PERSON] et al. presented an electrochemical biosensor by combining MBs-based immunoassay and SPE, modified with carbon black, with a portable potentiostat as a reader for SARS-CoV-2 detection in saliva (Figure 5B) [40]. In the MBs-based immunoassay, target protein (S or N protein) in the untreated saliva sample was selectivity captured by the respective monoclonal antibody-bound MB and sandwiched by the respective polyclonal antibody. A secondary antibody attached to the polyclonal antibody is labelled with an alkaline phosphate enzyme. In the electrochemical detection, the labelled beads were drop cast on the working electrode of SPE with 1-naphthyl phosphate to induce the formation of enzymatic by-product 1-naphth. The enzymatic reaction (enzymatic by-product) was electrochemically measured via differential pulse voltammetry (DPV) using a portable potentiostat. The sensor was tested using 24 clinical samples (positive and negative); the true positive rate was 100% and the true negative rate was 88.2% for detecting the S protein. The sensor required 30 min for reaction and exhibited the lowest detection limit of 19 ng mL\({}^{-1}\) for S proteins and 8 ng mL\({}^{-1}\) for N proteins, respectively. However, repeated incubation and washing steps are required to perform the MBs-based immunoassay prior to the electrochemical detection. [PERSON] et al. developed an ultrasensitive electrochemical biosensor (as shown in Figure 5C) based on multiplex isothermal rolling circle amplification (RCA) for rapid detection of viral N and S genes of SARS-CoV-2 [36]. The sensor works on a one-step strategy comprised of mixing capture probe-conjugated magnetic bead particle (CP-MBs), silica reporter probe (silica nanoparticles coated redox dye), and the target (viral N and S genes) in a single hybridisation step, followed by a single washing step.