The coronavirus disease (2019) pandemic, caused by the rapid outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed millions of lives worldwide. Scientists have developed various pharmaceutical and non-pharmaceutical measures to combat this pandemic. Among these, the development of effective vaccines, therapeutics, and fast and reliable diagnostic kits could aid immensely in managing the crisis. Nanotechnology has played a vital role during the pandemic. This article focuses on the role of carbon nanotubes in the development of biosensors to detect SARS-CoV-2.
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SARS-CoV-2 consists of a large positive-stranded genomic RNA that encodes accessory proteins and four structural proteins (spike, envelope, membrane, and nucleocapsid). The primary function of the S1 domain of the spike protein is to bind with the angiotensin-converting enzyme 2 (ACE2) of the host cell, while the S2 domain promotes fusion of the membranes, leading to infection.
This virus is extremely contagious, i.e., it is easily transmitted via touch, droplets, oral-fecal route, air contamination, from mothers to newborns, and from animals to humans. To prevent the further spread of the virus, early detection is extremely important.
Although real-time polymerase chain reaction (qPCR) has been recommended for the detection of SARS-CoV-2, this method requires expensive equipment, skilled personnel and is time-consuming. This inhibits early and rapid detection of the virus - a crucial aspect of COVID-19 treatment.
Carbon nanotube-based sensors have been developed, and they promise to be highly efficient and rapid diagnostic tools for SARS-CoV-2 infection.
Carbon Nanotubes (CNTs)
CNTs are carbon-based nanomaterials that possess many unique properties. They are hollow, nanometer-thick cylinders, which are incredibly stiff and durable due to carbon-carbon bonds.
CNTs are available in two forms: one atom thickness single-wall carbon nanotubes (SWCNTs) or multi-layers of graphite forming multi-wall carbon nanotubes (MWCNTs). They are thermally stable, naturally fluoresce when exposed to laser light, and possess electronic properties which have been exploited in the development of efficient sensors.
Detection of SARS-CoV-2 without Antibodies
Researchers from MIT have recently designed a novel sensor based on carbon nanotube sensor technology capable of rapidly detecting SARS-CoV-2 without requiring any antibodies or reagents.
The main advantage of this sensor is that it can avoid many time-consuming steps, such as the production of antibodies and purification. Researchers are confident that this new sensor will not only accurately diagnose COVID-19 but also detect other viruses that have the potential of causing future pandemics.
Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT, stated that rapid diagnosis could relax travel restrictions as people could be screened before boarding an airplane, and this could aid in preventing further spread of the virus.
Previously, researchers working at Strano’s laboratory claimed that sensors can be developed by wrapping CNTs in different polymers that respond to specific target molecules (biomarkers) by chemically recognizing them.
A new COVID-19 sensor, also known as Corona Phase Molecular Recognition (CoPhMoRe), is based on this approach.
CoPhMoRe contains amphiphilic polymers, where hydrophobic regions are present on the tubes like anchors, and hydrophilic regions form a series of loops extending away from the tubes.
The loop arrangement plays an important role, as only a specific type of target molecules can wedge into the spaces between the loops. This binding alters the intensity of the wavelength of fluorescence produced by the carbon nanotube. Early this year, Strano’s laboratory and InnoTech Precision Medicine (a Boston-based diagnostics tool company) received the National Institutes of Health grant to develop a CoPhMoRe biosensor to detect SARS-CoV-2 proteins.
Importantly, this sensor can detect both the nucleocapsid and the spike protein of the SARS-CoV-2. As stated above, this device is highly accurate and sensitive; it can detect 2.4 picograms of viral protein per milliliter of a sample within five minutes. Interestingly, this device can identify nucleocapsid protein in saliva samples.
The spike protein cannot be detected from the saliva sample because saliva contains carbohydrates and enzymes that interfere with protein detection - this is why most COVID-19 diagnostics require nasal swabs.
Detection of SARS-CoV-2 with Antibodies
Previous studies have shown that CNT network field-effect transistor (FET) electronic biosensors can effectively detect metal ions, biomolecules (hormones), viruses, and whole cells. Recently, scientists have developed a new electrochemical biosensor based on carbon nanotube field-effect transistor (CNT-FET) to detect the COVID-19 virus.
CNT-FET enables digital detection of the SARS-CoV-2 S1 antigens in saliva samples. As per the development of this biosensor, SWCNTs with the immobilization of anti-SARS-CoV-2 S1 antibody are deposited on the surface of SiO2 between the S-D (source-drain) channels using a linker 1-pyrenebutanoic acid succinimidyl ester (PBASE) via non-covalent interaction.
Researchers utilized RNA hybridization as the initial signal generator, and the liquid gated CNT network FET was used as the signal transducer. To develop this biosensor, researchers have used commercially available SARS-CoV-2 S1 antigen to analyze the electrical output of the CNT-FET biosensor.
This technology can efficiently distinguish SARS-CoV-2 from other coronaviruses that contain SARS-CoV-1 S1 or MERS-CoV S1 antigen. Additionally, it has proved to be highly sensitive and can rapidly detect COVID-19 infection using saliva samples.
CNT-based biosensors, both with or without antibodies, have shown high efficiency with respect to accurate and rapid detection of SARS-CoV-2. A rapid detection system would help separate infected and non-infected individuals and prevent the further spread of the COVID-19 infection.
Early diagnosis would promote SARS-CoV-2 treatment without delay. These diagnostic approaches are accurate, cheap, and a reliable alternative for existing diagnostic techniques.
Continue reading:Effect of Nano-Perovskite Structure on Suppressing the SARS-CoV-2 Infection.
References and Further Reading
Zamzami,A.M. et al. (2021) Carbon nanotube field-effect transistor (CNT-FET)-based biosensor for rapid detection of SARS-CoV-2 (COVID-19) surface spike protein S1. Bioelectrochemistry. 143. 107982. Available at: https://doi.org/10.1016/j.bioelechem.2021.107982
Thanihaichelvan, M. et al. (2021) Selective and electronic detection of COVID-19 (Coronavirus) using carbon nanotube field effect transistor-based biosensor: A proof-of-concept study. Materialstoday Proceeding. Available at: https://doi.org/10.1016/j.matpr.2021.05.011
Lim, Y. W. et al. (2021) Emerging Biosensors to Detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Review. Biosensors. 11(11), pp. 434; Available at: https://doi.org/10.3390/bios11110434
Trafton, A. (2021) Carbon nanotube-based sensor can detect SARS-CoV-2 proteins. Massachusetts Institute of Technology. [Online] Available at: https://news.mit.edu/2021/carbon-nanotube-covid-detect-1026
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