The incorporation of nanotechnology into medicine revolutionized both diagnostic and therapeutic technologies by enhancing their sensitivity and specificity capabilities. In light of the current coronavirus disease 2019 (COVID-19) pandemic caused by the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers have become increasingly interested in novel technologies that could help quickly diagnose viral infections.
In a recent Talanta review article, researchers discuss the contributions that have been provided by magnetic nanoparticles for the molecular diagnosis of human viruses.
Study: Contribution of magnetic particles in molecular diagnosis of human viruses. Image Credit: DC Studio / Shutterstock.com
Introduction
Nanotechnology-based techniques are adaptable and reliable in detecting diseases caused by viruses. Solid lipid nanoparticles, liposomes, inorganic nanoparticles, and polymeric nanoparticles are some of the most widely used advanced materials that are used in nanotechnology.
Nanoparticles allow researchers to conduct analyses at both cellular- and molecular-scale, which has supported their crucial role in various diagnostic advancements. For example, nanoprobes designed to recognize specific molecules have helped identify targets, even when present at low concentrations.
The present review focuses on the role of magnetic nanoparticles (MNPs) in identifying viruses, wherein the researchers provide insight into novel diagnostic methods that overcome many of the limitations associated with conventional diagnostic approaches.
Limitations of conventional systems
The technique used to diagnose the presence of a specific virus has often been specific to each virus; however, one of the most common assays includes the reverse-transcriptase polymerase chain reaction (RT-PCR). In addition to being the gold standard for diagnosing COVID-19, RT-PCR has also been used to detect the Marburg virus, Ebola virus, human immunodeficiency virus (HIV), hantavirus (HPS), influenza virus, and dengue virus.
In addition to RT-PCR, enzyme-linked immunosorbent assays, rapid antigen testing, immunofluorescence assays, and other forms of serological testing have also been used for conventional virus detection purposes.
Despite their clinical utility, many of these conventional techniques are associated with several limitations including the need for mass-testing kits, robust sensitivity capabilities, length completion requirements, and experienced personnel. For example, some of the requirements for RT-PCR in the diagnosis of COVID-19 include the refined extraction and accurate estimation of nucleic acids, which can lead to skewed results when performed by untrained personnel.
Furthermore, despite the availability of marketable kits that are easy to use, despite their high costs, and typically yield better ribonucleic acid (RNA) quality, accessibility to these kits during the pandemic was affected as a result of supply chain interruptions.
Taken together, there is a pronounced motivation to advance alternative diagnostic approaches that address these challenges, while also eliminating the hazard of handling live viruses and its associated biological safety requirements.
Nanoparticles in viral diagnosis
Many nanomaterials including MNPs, quantum dots (QDs), silicon nanowires (SiNWs), virus-like particles (VLPs), graphene, inorganic nanoparticles, liposomes, nanoparticles of self-assembled protein, polymers, and metal, silica nanospheres, as well as carbon nanotubes (CNTs), nanostructured surfaces and films are utilized for viral diagnostic purposes. Many of these nanomaterials are associated with unique properties including bioavailability, optimum tunable size, charge, shape, biodegradability, high surface plasmon resonance (SRP), photon exchange, superparamagnetism, luminescence, biocompatibility, immunocompatibility, and tolerability, all of which can be attractive characteristics for viral detection applications.
The ability to manipulate the surface of nanomaterials using functionalization chemistry further supports the utility of these materials useful for both diagnostic and therapeutic purposes.
Importantly, nano-based detection systems, along with extraction, offer several advantages as compared to conventional diagnostic approaches. These systems allow for the easy, rapid, highly sensitive, and label-free detection of viruses that will undoubtedly advance point-of-care (POC) nanodiagnostics in clinical practice.
MNPs and virus diagnosis
Among the numerous inorganic nanoparticles including gold, silver, and iron oxide that have been widely studied over the past several years, MNPs are often utilized for nucleic acid extraction, purification, and detection.
Some of the advantages associated with MNPs for these applications include their ability to magnetically control their accumulation, superparamagnetic behavior, inexpensive preparation, quick isolation inside buffer solutions, and sensitivity for signal detection of the signal. Taken together, these properties of MNPs allow for the purification, pre-concentration, and separation of nucleic acids to be completed quickly, all the while retaining specificity during the viral detection process.
MNPs also play an important role in real-time detection systems when combined with a fluorescent or chemiluminescent probe. For these applications, the morphology, functionalization, surface coating, and properties of MNPs are highly tunable, thereby allowing researchers to attach a wide range of groups to MNPs to increase their chemical functionality, constancy, wettability, and bonding adaptability for numerous applications.
MNPs in the diagnosis of COVID-19
Zinc ferrite (ZNF) MNPs functionalized by carboxylic group polymers, as well as multifunctional chitosan-coated lithium zinc ferrite MNPs integrated with graphene oxide MNPs (CHLZFO-GO MNC), have been used for the extraction of RNA to ultimately detect SARS-CoV-2 in patient samples.
By extracting viral RNA through these methods before the RT-PCR testing, researchers can effectively reduce the risk of false negatives. This type of advanced approach to RNA isolation from nasal swabs can also expand the ability to rapidly diagnose COVID-19 at much larger scales.
MNPs have also been studied for their ability to enhance the sensitivity of biosensing devices for the rapid detection of the SARS-CoV-2 spike protein and single-stranded RNA (ssRNA) obtained from biological samples including blood, urine, and serum. One such example is the giant magnetoresistive (GMR) biosensing device, which has the potential to provide quick and consistent detection of pathogens like SARS-CoV-2 to reduce the uncertainty during viral incubation periods.
Another biosensing application of MNPs for SARS-CoV-2 diagnostic purposes includes the use of functionalized MNPs, followed by a measurement of their magnetic response in an AC magnetic field. To this end, functionalized MNPs were used as sensors to detect mimic SARS-CoV-2 containing spike proteins that are bound with polystyrene beads, which allowed for a quick detection time that does not compromise on its sensitivity for SARS-CoV-2 detection.
To resolve some of the challenges associated with the labor-intensive requirements of current molecular analytical processes, MNPs that have been functionalized with poly (amino ester) bonded to carboxyl groups (pcMNPs) have been studied for RNA extraction techniques.
The complex of pcMNPs with RNA samples can immediately be used for RT-PCR reactions, thereby reducing the time constraints of this process to about 20 minutes. In addition to being a more rapid approach to RT-PCR analysis for COVID-19 diagnoses, this approach utilizing pcMNPs also provides a 10-copy sensitivity.
Conclusions
The present review provides insights into MNP strategies that have been designed for specific and non-specific viral diagnostic approaches. Importantly, various studies have looked to how MNPs can be incorporated into each step of the viral diagnosis process including extraction and purification to enrichment and detection of pathogens.