Catching it Early: New Ways of Detecting Coronavirus

Title: Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor

Author: Giwan Seo, Geonhee Lee, Mi Jeong Kim, Seung-Hwa Baek, Minsuk Choi, Keun Bon Ku, Chang-Seop Lee, Sangmi Jun, Daeui Park, Hong Gi Kim, Seong-Jun Kim, Jeong-O Lee, Bum Tae Kim, Edmond Changkyun Park, Seung II Kim

Journal: ACS Nano

DOI: 10.1021/acsnano.0c02823

Worldwide COVID-19 cases have now surpassed 5 million, with the death toll approaching 350,000. SARS-CoV-2 is the virus responsible for the disease and it was estimated that 1 infected person on average spreads the virus to 2.2 people.1 As there is no drug or vaccine available so far to immunize against SARS-CoV-2, early detection can prevent the spread of the disease. Current state-of-the-art methods for detection of the virus is reverse-transcription polymerase chain reaction or RT-PCR. RT-PCR involves isolation of viral RNA and converting it into DNA, followed by a chain of reactions. The whole process takes at least 3 hours and diagnostic accuracy can be affected by RNA preparation phase. Hence, there is a growing need for a method to detect SARS-CoV-2 rapidly and directly without sample preparation steps.

To bridge this gap, researchers from South Korea developed a transistor-based biosensor that can detect SARS-CoV-2 from human saliva swabs Transistor-based biosensors are generally composed of a transistor with a biosensitive layer on top that can detect analytes such as DNA and protein. When the analyte attaches to the biosensitive layer, a change in current is recorded across the transistor. Transistor-based biosensors are slowly gaining popularity due to their rapid results and low amount requirements for detection.

The SARS-CoV-2 virus has four different proteins: spike, envelope, matrix, and nucleocapsid. Among these four proteins, the ‘spike’ protein of SARS-CoV-2 has a unique structure compared to other closely related viruses such as MERS-CoV. Hence, it is generally used for detection of SARS-CoV-2. In this case, the biosensitive layer was formed using a SARS-CoV-2 spike antibody, which was immobilized onto the transistor surface using a linker (Figure 1). When a swab contains the SARS-CoV-2 virus, it gets attached to the transistor through interaction between the spike protein present in the virus and the antibody present on the transistor. This binding of the virus on the surface changes the output current of the transistor.

Figure 1. Schematic diagram of the transistor-based biosensor operation procedure. A swab from human is placed on the transistor that records change in current when the virus is present. Adapted with permission, Copyright 2020 American Chemical Society.

Researchers explored two main questions afterwards: What is the limit of detection and can this device selectively detect the spike protein of SARS-CoV-2 from other common coronaviruses. Figure 2a suggests that 1fg/mL (1 fg = 1/1015 g) of spike protein could be detected using this biosensor, which is well below the current standard detection technique. They also identified that in the presence of a spike protein of another coronavirus, MERS, this platform could selectively detect the spike protein of SARS-CoV-2 (Figure 2b). Once they established the sensitivity and specificity of this platform for the spike protein present in the virus, they tested the feasibility of the method for the actual virus. Upon using SARS-CoV-2 virus, this biosensor could detect very low concentration showing the potential for this biosensor to be used as a rapid and highly sensitive diagnosis platform.

Figure 2. a)  Transistor-based biosensor response in presence of different concentration of spike protein of SARS-CoV-2. b) Transistor-based biosensor response in presence of spike proteins of SARS-CoV-2 and MERS-CoV . (ΔI/I0) = (I – I0/I0), I = detected real-time current, I0 = initial current. Adapted with permission, Copyright 2020 American Chemical Society.

Finally, clinical samples were tested to analyze the performance of the biosensor. Human swab samples from a normal person and a COVID-19 patient were collected separately. The normal sample was loaded onto the device before the addition of the patient sample. Figure 3a clearly shows that patient samples produce a different signal from the normal sample within a couple of minutes. Even after diluting the patient sample 100000 times, clear responses were observed. This shows how little sample is required for diagnosis with this platform (Figure 3b).

Figure 3. a) Comparison of response signal from normal and patient signal. b) Detection of patient sample after dilution (dilutions from left to right: 1000000 times, 100000 times, 10000 times, 1000 times, and 100 times). Adapted with permission, Copyright 2020 American Chemical Society.

This work highlights the development of rapid detection technology for diagnosing cases of COVID-19.  Moreover, this concept could be extended to other viral diseases to facilitate early detection and improved outcomes for patients. However, more controlled experiments need to be carried out to increase the efficiency of detection for these types of biosensors. Hopefully, efforts like this from the scientific community will help people to tackle this crisis.

Reference

  1. Li, Q.; Guan, X.; Wu, P.; Wang, X.; Zhou, L.; Tong, Y.; Ren, R.; Leung, K. S. M.; Lau, E. H. Y.; Wong, J. Y.; Xing, X.; Xiang, N.; Wu, Y.; Li, C.; Chen, Q.; Li, D.; Liu, T.; Zhao, J.; Liu, M.; Tu, W.; et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N. Engl. J. Med. 2020, 382, 1199−1207.

 Cover image by Image by fernando zhiminaicela from Pixabay

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