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Ultrasensitive, New Design to SARS-CoV-2 Antigen Test

Novel research on the use of nanotechnology for electrochemical immuno-biosensing of the SARS-CoV-2 (COVID-19) antigen has emerged from the ACS Applied Materials and Interfaces journal. This study aims to advance current technology for the rapid diagnosis of COVID-19 infections.

Ultrasensitive, New Design to SARS-CoV-2 Antigen Test

Study: Highly Stable Buffer-Based Zinc Oxide/Reduced Graphene Oxide Nanosurface Chemistry for Rapid Immunosensing of SARS-CoV-2 Antigens. Image Credit: anyaivanova/

The Need for Innovative SARS-CoV-2 Diagnosis Technology

The severe acute respiratory coronavirus 2 (SARS-CoV-2) resulted in devastating infection rates worldwide and was established as a pandemic by the World Health Organization (WHO) in March 2020. This pandemic caused researchers and scientists around the world to focus on alleviating the burden of the virus by producing vaccines and focusing on diagnostic testing.

During the pandemic, the dependence on diagnostic testing has been tremendous with governmental policies being mandated for regular testing being required in order to aid with identifying the transmission of the virus.

The two diagnostic tests that were used the most for the SARS-CoV-2 virus consisted of the polymerase chain reaction test (PCR) as well as the ‘at home’ rapid lateral flow test.

Governmental health policies comprised of mandating regular testing with lateral flow kits, which were then required a PCR test follow-up if the lateral flow test was found to be positive or if the individual was experiencing cold or flu-like symptoms.

Those who were found to have positive test results were expected to self-isolate for approximately 10 days and this was to prevent the transmission of the virus to others, and this also comprised of staying home from work during this period of isolation.

The isolation period of those who were infected played a significant part in ensuring the safety of others who had not yet caught the infection as well as protecting vulnerable groups, such as the elderly and immunocompromised. These groups can be more susceptible to the virus and can also experience a longer and more severe recovery from the virus, leading to opportunistic infections and with really severe cases, even death.

The mortality rates for this infection have been high with more than five million deaths globally being recorded and so the need for accurate, reliable and fast detection of SARS-CoV-2 was considered to be significant.

Limitations of Current Detection Methods

The use of PCR tests for detecting this very transmissible virus is the gold standard method of diagnosis and detection; however, while this test is comprehensive and has effective sensitivity and specificity for the virus, it can also be inconvenient as this process can be time-consuming and laborious, which can make this test difficult to depend on with high demand such as during the pandemic.

Additionally, the use of the lateral flow tests has also been associated with limitations such as a lack of sensitivity, which translates to not being very effective for detecting the SARS-CoV-2 virus within all positive cases; this means positive patients who are using the lateral flow test may be given a false negative result. This investigation was carried out by the British Medical Journal (BMJ).

Novel Nanotechnology Detection Approach

The growing demand for rapid diagnostic methods for detecting the SARS-CoV-2 virus has been highlighted for its importance for controlling the spread of the infection and this can be advanced through the use of nanodiagnostics.

The use of electrochemical immuno-biosensors has been considered to be more ultrasensitive compared to optical methods for clinical detection of different viral diseases through identifying protein biomarkers. This can be due to their incorporation of label-free strategy and conductive nanostructures as well as their fast and high sensitivity, allowing effective diagnosis of infectious diseases. 

Additionally, electrochemical immuno-biosensors have previously been used for detecting the coronavirus and antigen biomarkers, with benefits such as a low limit of detection that allows for early diagnosis of disease. This method also allows for multiplex detection through the use of multichannel screen-printed electrodes which is useful for sensing more than one biomarker simultaneously.

The researchers of this study utilized nanomaterials to produce a highly sensitive electrochemical biosensor such as through a stable buffer-based zinc oxide/ reduced graphene oxide (bbZnO/rGO) nanocomposite that was coated on carbon screen-printed electrodes. This was used to detect the nucleocapsid protein (N) antigen of the SARS-CoV-2.

This research utilized a self-assemble L-cysteine crosslinker for the first time, to increase the functionality and sensitivity of the nanocomposite. The results of this study found a limit of detection of 21 fg/mL and sensitivity of 32.07 ohms·mL/pg·mm.

Translational Significance

The initial testing of this novel rapid detection method of the SARS-CoV-2 was successful for differentiating infected samples from the control groups and this demonstrates its reliability, as well as validating the use of the nanocomposite as an effective biosensor coating.

The future work of this research consists of evaluating its clinical performance with a larger cohort of COVID-19 patients to validate the reliability and accuracy of this nanotechnology biosensor.

It would also be useful to test the use of this biosensor technology for detecting other SARS-CoV-2 variants as well as other antigen biomarkers such as the spike protein that vaccines aim for as therapeutic targets.

The translational of this work would enable the sensing steps to be integrated into automated fluid-handling units that would be able to be used for sample-to-result tests that could be used by individuals in a similar manner to a lateral flow test.

With increased sensitivity and reliability and rapid testing, this novel biosensor technology could aid with easing the pandemic even with any new variants that could emerge.


Haghayegh, F., Salahandish, R., Hassani, M. and Sanati-Nezhad, A., (2022) Highly Stable Buffer-Based Zinc Oxide/Reduced Graphene Oxide Nanosurface Chemistry for Rapid Immunosensing of SARS-CoV-2 Antigens. ACS Applied Materials & Interfaces. Available at:

Further Reading

Yüce, M., Filiztekin, E. and Özkaya, K., (2021) COVID-19 diagnosis —A review of current methods. Biosensors and Bioelectronics, 172, p.112752. Available at:

BMJ. 2021. Covid-19: People are not being warned about pitfalls of mass testing. [online] Available at:

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Marzia Khan

Written by

Marzia Khan

Marzia Khan is a lover of scientific research and innovation. She immerses herself in literature and novel therapeutics which she does through her position on the Royal Free Ethical Review Board. Marzia has a MSc in Nanotechnology and Regenerative Medicine as well as a BSc in Biomedical Sciences. She is currently working in the NHS and is engaging in a scientific innovation program.


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