## 2 Latest Developed Biosensors for COVID-19
### Field Effect Transistor (FET) Biosensor
#### 2.4.1 FET Biosensor for COVID-19  
Attachment of carbon-based two-dimensional materials and nanotubes (CNTs) on the surface of FET biosensors have been explored to enhance the detection of the target analyte. CNTs and graphene-based FETs have shown high sensitivity in detecting small concentrations of target analyte [104; 105]. Recently, a FET biosensor was developed by depositing SARS-CoV-2 spike protein and anti-nucleocapsid protein antibodies functionalised single-walled carbon nanotube (SWCNT) on the sensor surface to detect complimentary SARS-CoV-2 antigens (Figure 8A) [99]. Based on 28 positive samples, the SWCNT-based FET biosensor exhibited a true positive rate of 82.1% and 53.6% for detecting spike protein and nucleocapsid protein, respectively. Based on 10 negative samples, the true negative rate was 70% for both proteins. Overall, the SWCNT-based FET sensor exhibited excellent sensitivity with a LOD of 0.55 fg mL\({}^{-1}\) and 0.016 fg mL\({}^{-1}\) in detecting spike protein and nucleocapsid protein, respectively [99]. The sensor has the potential to be used as a rapid SARS-CoV-2 antigen test using clinical nasopharyngeal samples, without pre-processing, in less than 5 min. In another approach, SARS-CoV-2 spike protein antibodies were functionalised on graphene sheets, which were then deposited on the sensor surface. This graphene-based FET biosensor is depicted in Figure 8B. The sensor was able to detect the SARS-CoV-2 spike antigen protein down to fg mL\({}^{-1}\) in phosphate-buffered saline samples or clinical transport medium and with a LOD of 2.42 \(\times\) 10\({}^{2}\) copies mL\({}^{-1}\) in clinical samples, at a response rate between 0 and 400 s [42]. However, for viral detection of SARS-CoV-2, the RNA probe is required to detect the presence of complementary nucleic acid sequences (target sequences). To fulfil this need, recently a liquid gated CNT network FET was fabricated on a flexible Kapton film [100], as shown in Figure 8C. The sensor was able to selectively detect a portion of the SARS-CoV-2 RNA through hybridisation. Here, the reverse sequence of the RNA-dependent RNA polymerase gene of SARS-CoV-2 was immobilised onto the CNT sidewalls. The RNA hybridisation was used as the primary signal generator and the liquid gated CNT network FET was used as the signal transducer. The biosensor showed a selective sensing response to the target sequence with a LOD of 10 fM. Figure 7: **(A)** Field-effect transistor (FET)-based biosensor with a \(p\)-type semiconductor channel. **(B)** (i)** Negatively charged target molecules captured by the biorecognition elements accumulate positive charge carriers (holes) in the channel, which increases the current from the source to the drain electrode. **(ii)** If positively charged target molecules bind with the biorecognition elements, the holes are depleted and the current decreases. In another remarkable FET biosensor, gold nanoparticles (AuNP) decorated graphene sheets and phosphorodiamidate morpholino oligos (PMO) probes were employed on the sensor surface for ultrasensitive and rapid SARS-CoV-2 detection (Figure 8D) [106]. The PMO probe is usually 25 bases in length, and they bind to complementary sequences of RNA or single-stranded DNA according to standard nucleic acid base-pairing [107]. The PMO enabled direct detection of SARS-CoV-2 RNA through the hybridisation between the PMO probe and SARS-CoV-2 RdRp without the need for further PCR amplification. For clinical readiness, an FET biosensor needs to have good reusability [108]. For SARS-CoV-2 RdRp detection, this sensor can be chemically regenerated for reuse by denaturing the PMO-RNA duplex with 8.3 M urea solution for 5 min. The high surface-area-to-volume ratio of AuNP, high conductivity of graphene, and high density of neutral PMO immobilisation provided more responsive testing than using charged oligonucleotide capture probe (e.g., single-stranded DNA probe) [106] for RNA detection.