With the invention of SELEX in 1990, scientists have been able to identify high-affinity aptamers, artificial oligonucleotides (DNA or RNA), that serve as molecular probes for disease biomarkers. In decades since SELEX was developed, researchers have established a number of platforms that convert target-aptamer into detectable signals. These biosensors that employ aptamers are known as aptasensors.
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Already, aptasensors have helped advance the field of clinical diagnostics and many more technologies are currently under development. The potential to identify diagnostic biomarkers is, theoretically, unlimited. Therefore, there is a potential to leverage aptasensors into diagnostic tools for a vast range of diseases in a diverse set of patient groups. Currently, aptasensors are most important to the fields of clinical diagnostics in oncology and infectious disease (including viruses).
Here, we give an overview of how aptasensors work, how they are currently being used, and how applications of aptasensors may develop in the future.
How do Aptasensors Work?
Aptamers are engineered, artificial oligonucleotides (DNA or RNA). They are designed to bind to specific targets with high affinity and specificity. Aptamers that have been successfully developed target a wide selection of protein families, such as cell-adhesion molecules, cell-surface receptors, cytokines, kinases, and proteases.
The most simple aptasensors work by inducing a detectable electrochemical signal when they bind with their target; these are known as electrochemical aptasensors. These sensors have high sensitivity, which can further be increased via the attachment of biocatalytic labels to the aptamer-target complexes, thus enhancing the detection signal. Additionally, these systems are relatively low-cost and do not require labeling systems.
The other major class of aptasensors is optical aptasensors. Unlike electrochemical aptasensors, optical aptasensors can require labels (depending on the platform), such as fluorescence, luminophore, enzyme, nanoparticles. Label-free systems include SPR and optical resonance. However, most optics methods rely on labels, using optical detection methods such as colorimetry, chemiluminescence, and fluorescence to detect targets. In recent years, this list has expanded to include non-conventional optical methods, e.g. surface plasmon-coupled directional emission (SPCDE).
Applications of Aptasensors
Aptasensor applications have significantly impacted the field of clinical diagnostics. To date, there are numerous aptasensor platforms that are being used to detect cancer, cardiovascular disease, infectious disease, and viral disease. In the future, we will likely see this list of diagnostic applications grow.
Aptasensors in Cancer Diagnostics
Aptamers have been widely adopted in cancer diagnostics. They are one of several newly emerging approaches to cancer diagnostics that are causing excitement in the field. Traditional diagnostic methods in oncology have failed to be sensitive enough to diagnose most cancers early enough for treatment to be administered when it has its greatest chance to be effective.
Early access to therapy is vital to increasing overall survival in cancer; therefore, one of the best ways to combat the disease is with highly sensitive and reliable diagnostic tests. Enter aptasensors, which are not only sensitive, but also quick, simple, low-cost, and often deliverable via portable platforms.
Aptasensor applications in oncology are also making it possible to improve the target specificity and pharmacokinetic profiles in drug delivery systems.
Aptasensors in Cardiovascular Disease Diagnostics
Cardiovascular disease is a major cause of death around the world and is a significant burden on health systems. Like cancer, early detection of cardiovascular is important to disease outcomes. The earlier the disease is detected, the more likely it is that therapeutics will be effective and reduce the health complications that are associated with cardiovascular disease, as well as reduce the likeliness of death.
Aptasensors have been developed that offer improved sensitivity and specificity compared with traditional diagnostic techniques. Developments in this field have been particularly reliant on innovation in nanoscience. Many aptasensor platforms for cardiovascular disease leverage nanomaterials in some way.
Aptasensors in Infectious and Viral Disease Diagnostics
Conventional diagnostic tools for detecting viral and bacterial disease are often time-consuming, expensive, and have considerable resource demands (both for equipment and trained members of staff). Aptamers could provide a faster and more cost-effective solution, easily discriminating between virus serotypes, and are ideal for sensing applications.
Research has shown that aptamers can specifically bind to flaviviruses and their protein products, such as Ebola, Zika, dengue virus, severe acute respiratory syndrome (SARS), Escherichia coli, various species of salmonella including S. enteritidis and S. enterica, and various species of staphylococcus including S. aureus, S. typhimurium, and S enteritidis. Finally, studies have shown that aptamers can also bind to HIV-1 and hepatitis C virus. Therefore, there is great potential to develop aptasensors to establish diagnostic tools for a wide range of infectious diseases.
It is likely that as research into aptamers continues, more diagnostic tools will be developed based on aptasensors. These tools will likely be more accurate, faster, and cost-effective than current tools. Aptaensors have the potential to transform clinical diagnostics across cancer, cardiovascular disease, infectious and viral disease, and more.
References and Further Reading
Azzouz, A., Hejji, L., Sonne, C., Kim, K. and Kumar, V., 2021. Nanomaterial-based aptasensors as an efficient substitute for cardiovascular disease diagnosis: Future of smart biosensors. Biosensors and Bioelectronics, 193, p.113617. https://www.sciencedirect.com/science/article/abs/pii/S0956566321006540
Hong, P., Li, W. and Li, J., 2012. Applications of Aptasensors in Clinical Diagnostics. Sensors, 12(2), pp.1181-1193. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304108/
Ilgu, M., Fazlioglu, R., Ozturk, M., Ozsurekci, Y. and Nilsen-Hamilton, M., 2019. Aptamers for Diagnostics with Applications for Infectious Diseases. Recent Advances in Analytical Chemistry,. https://www.intechopen.com/chapters/66038
Sharma, A., Dulta, K., Nagraik, R., Dua, K., Singh, S., Chellappan, D., Kumar, D. and Shin, D., 2022. Potentialities of aptasensors in cancer diagnosis. Materials Letters, 308, p.131240. https://www.sciencedirect.com/science/article/abs/pii/S0167577X21019388
van den Kieboom, C., van der Beek, S., Mészáros, T., Gyurcsányi, R., Ferwerda, G. and de Jonge, M., 2015. Aptasensors for viral diagnostics. TrAC Trends in Analytical Chemistry, 74, pp.58-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112930/
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