Diagnostics is a critical weapon in the fight against this pandemic, as it is pivotal to isolate infected individuals as early as possible, preventing dissemination17. Several nanotechnology-based approaches for SARS-CoV-2 tagging and detection are being developed (Fig. 2).
Nanomaterials functionalized with nucleic acids or antibodies represent the main lines of nano-based detection, via colorimetric or antigen-binding assays, as well as light and photothermal platforms. Ab, antibody; FRET, Förster resonance energy transfer; LSPR, localized surface plasmon resonance; NPs, nanoparticles; PNA, peptide nucleic acid; PPT, photothermal therapy.
Generally, testing kits operate based on detection of antibodies (by enzyme-linked immunosorbent assay, or enzyme-linked immunosorbent assay (ELISA)) or RNA (by polymerase chain reaction, or PCR) associated with the virus (from nasopharyngeal swabs taken from individuals’ noses and throats). This relies on their surface interactions with a complementary detection ligand or strand in the kit18. However, these testing kits are generally associated with problems such as false-negative results, long response times and poor analytical sensitivity19. To this end, due to their extremely large surface-to-volume ratios, nanosized materials can instigate highly efficient surface interactions between the sensor and the analyte, allowing faster and more reliable detection of the virus20. Accordingly, a group of researchers have developed a colloidal gold-based test kit that enables easy conjugation of gold nanoparticles to IgM/IgG antibodies in human serum, plasma and whole blood samples21. However, the targeted IgM/IgG antibodies in this kit were not specific to COVID-19, and as a result in some cases produced false results associated with patients who were suffering from irrelevant infections. Consequently, researchers from the University of Maryland, USA, developed a colorimetric assay based on gold nanoparticles capped with suitably designed thiol-modified DNA antisense oligonucleotides specific for N-gene (nucleocapsid phosphoprotein) of SARS-CoV-2, which were used for diagnosing positive COVID-19 cases within 10 min from the isolated RNA samples22. Such testing kits could potentially produce promising results, however their performance would still be affected by quantity of the viral load. To address this shortcoming, researchers from ETH, Switzerland, have recently reported a unique dual-functional plasmonic biosensor combining the plasmonic photothermal effect and localized surface plasmon resonance (LSPR) sensing transduction to provide an alternative and promising solution for clinical COVID-19 diagnosis23. The two-dimensional gold nano-islands functionalized with complementary DNA receptors provide highly sensitive detection of the selected sequences from SARS-CoV-2 through nucleic acid hybridization. For better sensing performance, thermoplasmonic heat is generated on the same gold nano-islands chip when illuminated at their plasmonic resonance frequency. Remarkably, this dual-functional LSPR biosensor exhibited high selectivity towards the SARS-CoV-2 sequences with a detection limit as low as 0.22 pM. In other work, to achieve rapid and accurate detection of SARS-CoV-2 in clinical samples, researchers from the Korea Basic Science Institute developed an ultra-sensitive field-effect transistor (FET)-based biosensing device24. The sensor was produced by coating graphene sheets of the FET with a specific antibody against SARS-CoV-2 spike protein. The FET device could detect the SARS-CoV-2 spike protein at concentrations of 1.31×10–5 pM in phosphate-buffered saline and 1.31×10–3 pM in clinical transport medium. Remarkably, the device exhibited no measurable cross-reactivity with Middle East respiratory syndrome coronavirus (MERS-CoV) antigen, indicating the extraordinary capability of this sensor to distinguish the SARS-CoV-2 antigen protein from those of MERS-CoV.
Another approach that can be used for SARS-CoV-2 and that was successfully used with MERS-CoV, Mycobacterium tuberculosis and human papillomavirus consists of a paper-based colorimetric sensor for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced silver nanoparticle aggregation25. Briefly, in the absence of complementary DNA, silver nanoparticles aggregate due their electrostatic interactions with the acpcPNA probe. However, in the presence of target DNA, a DNA–acpcPNA duplex starts to form which leads to dispersion of the silver nanoparticles as a result of electrostatic repulsion, giving rise to a detectable colour change25. The use of aptamers and molecular beacons instead of PNA can also represent a potential alternative.
Other avenue where nanomaterials can contribute to detection of SARS-CoV-2 is the extraction and purification of targeted molecules from biological fluids (blood and nasal/throat samples). Thus, nanomaterials with magnetic properties can be decorated with specific receptors of the virus, leading to attachment of virus molecules to the nanoparticles that will allow their magnetic extraction using an external magnetic field.
In this way nanomaterial-based detection can facilitate faster and more accurate detection of the virus even at early stages of the infection, in large due to versatility of surface modification of nanoparticles.
