## 2 Latest Developed Biosensors for COVID-19  
Compared to time staking laboratory tests, a biosensor with fast response and high accuracy in the form of a point-of-care device would be an excellent aid for the early diagnosis of SARS-CoV-2 infection. As shown in Figure 1A, generally a biosensor comprises of biosensing elements such as nucleic acids, enzymes, or antibodies that can interact with the target analyte in the form of biological or chemical sample, a transducer that can convert the changes in the biosensing element to an electrical signal, and an amplifier and necessary electronic system to process the electrical signal to digitise the output [27; 32]. The COVID-19 outbreak has spurred the development of various types of biosensors with different biosensing platforms that can be used for the diagnosis of COVID-19.  
SARS-CoV-2 contains four structural proteins, spike (S), membrane (M), envelope (E) and nucleocapsid (N) proteins, as shown in Figure 1B. The S protein is composed of two subunits S1 and S2, which are responsible for the attachment, fusion and entry of the virus. The S1 subunit contains a receptor-binding domain (RBD) that recognises host cell receptors and human angiotensin-converting enzyme 2 (ACE2). The S2 subunit facilitates membrane fusion for virus entry. N proteins bind to the viral RNA genome to form the nucleocapsid. M proteins release nutrients at the transmembrane and form the viral envelope. E proteins are small polypeptides that are responsible for the assembly and release of the virus. The SARS-CoV-2 viral RNA genome consists of open reading frames (ORFs) genes, which encode a total of 16 non-structural proteins (e.g., ORF1 ab gene), and at least four structural proteins (e.g., S gene, E gene, M gene, N gene) [33; 34]. For SARS-CoV-2 detection, three types of diagnostic tests--on nasopharyngeal swab, throat  
Figure 1: (**A**) Schematic diagram of a biosensor. (**B**) Structure and function of SARS-CoV-2 virus. The main four viral surface proteins are Spike (S), Envelope (E), Membrane (M) and nucleocapsid (N). S protein contains the receptor-binding domain (RBD) that recognises the host cell receptor, i.e., the human angiotensin-converting enzyme 2 (ACE2). E protein contributes to the assembly and morphogenesis of virions. M protein, which is embedded in a lipid bilayer, is responsible for the release of nutrients at the transmembrane and form the viral envelope. N protein binds to the RNA genome to form the nucleocapsid. **Preferred target analyte used for current COVID-19 biosensor development.  
swab, blood and saliva samples--have been widely used based on (i) virus detection--hybridisation between sequence complementary (capture probe) to the target RNA genome, (ii) antigen protein detection--interaction of monoclonal antigen-specific antibody and virus antigen protein and (iii) antibody detection--interaction of recombinant antigen and target neutralising antibody. As described in the following sections, the current development of biosensors employs these approaches to target SARS-CoV-2 RNA genome (ORF1 ab gene, RNA-dependent RNA polymerase (RdRP) gene, S gene, N gene) [35; 36; 37; 38], specific antigen protein (S protein (S1 subunit/RBD), N protein) [39; 40; 41; 42] and neutralising antibody (IgM, IgG) [35; 43].