The rising rate of infectious diseases with unidentified origins and ongoing mutations has emerged as a global threat. Identifying the microorganisms that cause these diseases rapidly and precisely is crucial, as doing so will allow for early disease diagnosis, transmission control, and therapy. This article focuses on employing carbon nanotubes for biosensing and imaging in infectious diseases.
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Conventional Methods For Detecting Infectious Disease
Infectious diseases can be spread through viruses, fungi, bacteria, and parasites. In the twenty-first century, infectious epidemic outbreaks have occurred repeatedly, including those caused by the Ebola virus and the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).
Chemi-luminescent immunoassays (CLIA), polymerase chain reactions (PCR), enzyme-linked immunosorbent assay (ELISA) and culture for microbe isolation and identification procedures are currently the most widely utilized clinical diagnostic methods in infectious disorders.
The main drawbacks of conventional approaches comprise their cost, time-consuming nature, low level of pathogen/microorganism specificity, and inapplicability for on-site monitoring.
Thus, it is crucial to develop novel biosensing and imaging approaches to accomplish early diagnosis of infectious disorders. This will result in early treatment of the patient's symptoms and effective pandemic and epidemic outbreak prevention.
Applying Nanomaterials to Biosensing and Imaging
Current research aims to create novel nanomaterials with distinctive features for the advancement of detection methods. Carbon nanomaterials (CNs), in particular, have attracted immense interest in both material biomedical applications and science.
Carbon nanotubes (CNTs), fullerenes, graphene oxide (GO) and graphene, and carbon dots (CDs) are examples of CNs, which belong to the family of carbon compounds.
They offer excellent structural, chemical, and physical features, including a large surface area, good electrical and mechanical strength. The three main biomedical applications of CNTs are gene/drug delivery, biosensing, and bioimaging.
Benefits of Carbon Nanotubes
Carbon nanotubes (CNTs) are uniform structures made of one or more layers of carbon atoms. Depending on how many layers are present, CNTs are categorized as either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs).
Numerous recent studies have employed CNTs due to their excellent mechanical strength due to the presence of sp2 hybridized carbon atoms. Additionally, when the typical wall number is close to 2.7, CNTs exhibit promising electrical conductivity.
When employed for disease identification, CNTs can bind finely dispersed nanoparticles to their surface, thereby increasing the electro-active surface area and improving the sensitivity and selectivity of electrochemical sensors used for biosensing in infectious diseases.
Another advantage of some CNT varieties is their ability to absorb photons in the visible and near-infrared (NIR)-I window with fluorescence in the NIR-II window. This characteristic has led to the development of novel and advanced bioimaging techniques.
Recent Research Using Carbon Nanotubes
Bardhan et al., reported using single walled carbon nanotubes as probes for imaging pathogenic or bacterial infections in an article published in “Nature communications”.
They developed F′-positive and F′-negative bacterial strain-distinguishing functionalized SWNTs, utilizing the M13 bacteriophage and an anti-bacterial antibody. The method is employed to identify intramuscular Staphylococcus aureus (S. aureus) infections and to image S. aureus infective endocarditis.
Numerous biosensing investigations have also been carried out by scientists to research the early diagnosis of infectious diseases that can propagate into becoming pandemics. A recent work published in the journal "Analytical Chemistry - ACS Publications." reported the fabrication of a fluorescent SWCNTs-based nanosensor for antibody-free, quick detection of SARS-CoV-2 proteins.
The SARS-CoV-2 spike (S) and nucleocapsid (N) proteins are recognized by the nanosensor's special three-dimensional nanosensor interfaces, which are composed of poly(ethylene glycol) (PEG) and phospho-lipid hetero-polymers adsorbed on near-infrared (nIR) fluorescent SWCNTs.
The SWCNT-based sensor demonstrated ≤ fifty percent sensor responses within five minutes of injecting viral protein. The limit of detections for S and N proteins was recorded as 350 pM and 48 fM, respectively.
In another study, it was discovered that the gold nanoparticle (AuNPs) and carbon nanotube (CNT) nanocomposite had more catalytic activity than CNTs or AuNPs alone towards the oxidation of tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2). The described nanocomposites have been employed in an immunosensor to detect the influenza A (H3N2) virus with sensitivity ≤ 10 PFU mL-1.
Ma et al. and Cui et al. proposed the use of molecularly imprinted polymers (MIPs) in conjunction with a MWCNT-based biosensor for the sensitive detection of human immunodeficiency virus-p24 (HIV-p24) and other infectious illnesses.
Glassy carbon electrodes (GCEs) modified via surface polymerization was used by Ma et al. to establish a rapid and selective approach to identify HIV-p24. The proposed biosensor revealed a LOD of 0.083 pg cm−3 (S/N = 3). These studies showcase the successful incorporation of carbon nanotubes in biosensing and imaging tools for infectious diseases.
Future Outlook
The adoption of carbon nanotubes in biomedicine has been promoted by critical variables such as the emergence of pandemic infectious disease outbreaks and the necessity of earlier detection of disorders that are challenging to treat.
Several diagnostic techniques have been invented based on CNTs, including bioimaging contrast agents, nucleic-acid amplification tests (NAAT) enhancers to detect pathogenic genes and biosensors. These diagnostic technologies have a lot of potential, but a few issues still need to be resolved before they can be used in infectious disease diagnosis.
Key issues such as the stability of the developed analytical approach, standardization of materials, and the toxicity of carbon nanotubes, when used as in-vivo imaging contrast agents, are likely to be the focus of future research.
References and Further Reading
Cho, S. Y., Jin, X., Gong, X., Yang, S., Cui, J., & Strano, M. S. (2021). Antibody-Free Rapid Detection of SARS-CoV-2 Proteins Using Corona Phase Molecular Recognition to Accelerate Development Time. Analytical Chemistry, 93(44), 14685–14693.
He, Y., Hu, C., Li, Z., Wu, C., Zeng, Y., & Peng, C. (2022). Multifunctional carbon nanomaterials for diagnostic applications in infectious diseases and tumors. Materials Today Bio, 14, 100231. https://doi.org/10.1016/J.MTBIO.2022.100231
Meskher, H., Mustansar, H. C., Thakur, A. K., Sathyamurthy, R., Lynch, I., Singh, P., Han, T. K., & Saidur, R. (2023). Recent trends in carbon nanotube (CNT)-based biosensors for the fast and sensitive detection of human viruses: a critical review. Nanoscale Advances, 5(4), 992–1010. https://doi.org/10.1039/D2NA00236A
Sheikhzadeh, E., Beni, V., & Zourob, M. (2021). Nanomaterial application in bio/sensors for the detection of infectious diseases. Talanta, 230, 122026. https://doi.org/10.1016/J.TALANTA.2020.122026
Bardhan, N. M., Ghosh, D., & Belcher, A. M. (2014). Carbon nanotubes as in vivo bacterial probes. Nature Communications 2014 5:1, 5(1), 1–11. https://doi.org/10.1038/ncomms5918
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