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Viruses are particulate and exist in different morphological forms. The small size (20 to 900 nm) of viruses increases the difficulty of their isolation and visualization compared to other microbes.
Viruses are usually highly contagious and the absence of immediate and efficient control systems is the main reason behind their potential health impacts. Nanotechnology has proved to be efficient in laboratory diagnosis of infections in general and viral infections in particular.
Evolution in Virus Detection Techniques
In 1950, with the development of a cell culture system and electron microscope, the first virus isolation and detection were started. In the early 1980s, diagnostic virology made major advancements with the invention of immunoassays and polymerase chain reaction (PCR).
The rapid development of a wide range of serological and molecular detection techniques was a boon to both laboratory research and the clinical diagnosis of viruses. Currently, the unique properties of nanomaterials (physical, chemical, mechanical, magnetic, etc.) are effectively used in virus detection.
Nanoparticles used in Virus Detection
Several nanomaterials such as quantum dots, carbon nanotubes, graphene oxide, silica, and metal nanoparticles are used as biosensors for the detection of the pathogenic virus. Some of the nanoparticles used in virus detection are discussed below.
Quantum Dots (QDs)
QDs are nanoscale semiconductor crystals with unique optical and electrical properties.
QDs have a wide absorption range, photoluminescence, multiplexed staining, long florescent lifetime and high resistance to photobleaching. QDs are useful tools for providing rapid and sensitive virus detection to facilitate early treatment and monitoring of viral disease.
- QDs-based rapid capture and imaging system involves a dual-stain imaging technique. This technique is capable of capturing and detecting Human Immunodeficiency Virus (HIV) at a high speed and is also extremely cost-effective.
- FRET-based QDs-DNA system is used for rapid, easy, and sensitive detection of Hepatitis B Virus-DNA.
Carbon Nanomaterials
Carbon Nanotubes (CNTs): CNT-based biosensors have high sensitivity and selectivity due to their high surface area. This system is also beneficial for its easy functionalization and immobilization of nanoparticles. It is used to detect hepatitis B and papillomavirus.
Silica Nanoparticles (SiNPs): Many biomolecules could be linked to silica nanoparticles, including antigen-antibodies, peptides and DNA, and that, subsequently, makes them important for bioanalytical research. This system is used for the detection of Hepatitis B Virus (HBV).
Metal and Metal Oxide Nanoparticles
Silver Nanoparticles (AgNPs): The fluorescent characteristics of AgNPs provide high sensitivity to optical biosensors. The optical-based biosensor is used for the detection of viruses like HIV and HBV.
Magnetic Nanoparticle (MNPs): MNPs are used to detect surface glycoprotein hemagglutinin (HA) from the Influenza A virus (FLUAV) H5N1. Amino functional carbon-coated MNPs have been used to distinguish the hybridization of HBV nucleic acids.
Aluminum Nanoparticles (AlNPs): Nanoporous morphology is the most prominent feature that attracts biosensing scientists to AINPs. One of the advantages of having a porous structure is the increase in surface to volume ratio that results in an increased number of target molecules inside nanopores. Researchers have used nanoporous alumina for the detection of dengue virus.
Gold Nanoparticles (AuNPs): AuNPs have been extensively used in the field of virus detection owing to their unique optical and electrical properties.
- Hantaan Virus (HTNV): Rodent-borne HTNV can cause hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome in humans. A novel immuno-PCR assay has been developed using AuNP for the immunological detection of HTNV nucleocapsid protein. This assay could optimally detect low concentrations of purified or spiked antigen samples.
- Rift Valley Fever Virus (RVFV): RVFV infected persons develops retinitis, encephalitis, and paralysis. A novel immunoassay based on AuNPs coupled with a surface-enhanced Raman scattering (SERS) technique has been developed for the detection of RVFV capsid antigen.
- Severe Acute Respiratory Syndrome (SARS): Coronaviruses are enveloped RNA viruses that are pleomorphic in shape. Coronaviruses are clinically significant to humans and usually associated with different respiratory, intestinal, hepatic, or neurological diseases. Coronaviruses, such as SARS-CoV identified in China in 2002 and MERS-CoV discovered in the Middle East in 2012, are notorious pathogens able to cause widespread outbreaks of pneumonia and pneumonia-like conditions with very high morbidity and mortality rates of up to 35%. SARS detection using AuNPs is primarily focused on developing rapid and specific molecular detection through colorimetric assay (pp1ab gene detection) and electrochemical assay (nucleocapsid protein gene detection).
- Dengue Virus (DENV): DENV is now known to be an epidemic in more than 100 subtropical and tropical countries, threatening up to 2.5 billion people. AuNPs combined with Quartz Crystal Microbalance (QCM) and Inductively Coupled Mass Spectrometry (ICP-MS) is used to develop two novel molecular assays for DENV detection.
- Hepatitis E Virus (HEV): HEV causes human liver inflammation called hepatitis E, which is widely spread in developing countries with poor hygiene conditions. AuNP-based colorimetric assay has been reported for the molecular detection of HEV.
- Kaposi’s Sarcoma-associated Herpesvirus (KSHV): KSHV/HHV-8 is a leading cancer-causing virus. It is commonly responsible for a range of neoplastic diseases in immunocompromised patients, such as Kaposi sarcoma, primary effusion lymphoma, and Castleman disease. With the combination of AuNPs and AgNPs, a colorimetric assay has been designed for one-pot molecular detection of KSHV.
- Influenza A Virus (IAV): Several strains of influenza virus cause acute respiratory diseases that are highly contagious. Detection of IAV focuses on developing assays that enable the direct detection of whole IAV particles or viral RNA through numerous AuNP-based fluorometric, SERS, light-scattering, colorimetric, and electrochemical processes.
- Human Papilloma Virus (HPV): HPV infects the deepest layer of the skin or the genital surfaces. AuNPs were used as an immobilization scaffold for DNA immobilization on a silicon substrate carrying nanogapped interdigitated electrodes in the electrical detection of HPV.
- Human Immunodeficiency Virus (HIV): HIV infection is correlated with the development of AIDS, a disease that destroys the immune system causing the entire body to become vulnerable to life-threatening infections. AuNPs assays can be very beneficial in detecting HIV early which can prevent its spreading.
The use of nanoparticles as a marker for the rapid and accurate detection of infectious agents in small sample volumes helps in early detection at an affordable cost.
References and Further Reading
Mokhtarzadeh, A. et al. (2017). Nanomaterial based biosensors for detection of pathogenic virus. TrAC Trends in Analytical Chemistry. 97, 445-457.
Shehata Draz, M. and Shafiee, H. (2018). Applications of gold nanoparticles in virus detection. Theranostics. 8, 7, 1985-2017.
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