Life Sciences Discovery and Technology Highlights

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease that causes severe respiratory distress. The COVID-19 reproductive number is highly infectious, spreading to ≥2.2, yet no drugs or vaccines are available. SARS-CoV-2—the virus causing COVID-19— has been found to be more similar to SARS-CoV than MERS-CoV (Middle East respiratory syndrome coronavirus). Like SARS-CoV, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for efficient cell entry. SARS-CoV-2 uses its spike (S) protein to bind with the ACE2 for efficient cellular entry. Currently, real-time reverse transcription (RT) PCR is the chief method to detect SARS-CoV-2. RT-PCR requires the extraction of viral RNA, taking at least 3–4 h to process. It has several limitations, including the requirement for RNA preparation that could affect diagnostic accuracy. Field-effect transistor (FET) biosensing can sensitively and instantaneously measure minute quantities of analytes. Graphene-based FET biosensors can detect changes on their surface, allowing ultrasensitive and low-noise detection, making it attractive for sensitive antibody-based diagnosis. The authors develop a FET biosensor by functionalizing graphene with anti-S antibodies. Prior to functionalizing, the anti-S antibody enabled detection of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA), but not the MERS-CoV S protein or bovine serum albumin (BSA), up to a detection limit (LOD) of 4 ng/mL. Successful immobilization of antibodies resulted in a decrease in the currentvoltage slope characteristics. Further characterization suggests that FET biosensing provides reliable detection signal characteristics for their target analytes. The FET biosensor was ultrasensitive, able to detect as low as 1 fg/mL of SARS-CoV-2 S protein in saline solution, which was substantially lower than detection using an ELISA format. Removal of the antibody and MERS-CoV S proteins generated negligible signal—demonstrating the specificity of the FET biosensor. The authors then propagated SARSCoV-2 in culture, demonstrating an LOD of 16 PFU/mL with 4 logs of linear signal response. Finally, the authors compared samples from infected and uninfected individuals in diluted samples containing as few as 242 copies/mL. Further optimization would be necessary to reduce signal noise. Thus, the FET biosensor is suitable for SARS-CoV-2 detection over a large dynamic range without sample processing. Such biosensing technologies show sufficient specificity and sensitivity and could be adapted to identify emerging infectious disease threats. (Seo, G.; et al. ACS Nano 2020, 14, 5135–5142.)