A Biosensor Has Been Developed That Can DETECT the Novel Coronavirus IN THE AIR

The novel coronavirus can be detected using a newly developed biosensor (biological detector), it has been announced. In the future, this biosensor could be used to measure virus concentrations in enclosed places with large numbers of people or in hospitals.

Researchers at Empa, ETH Zurich and the University of Zurich generally study the measurement, analysis and reduction of air pollutants such as aerosols and artificially produced nanoparticles. However, the whole world is currently facing the COVID-19 Pandemic, which is also changing the goals and strategies of laboratories previously working in different fields. The new focus: a sensor that can rapidly and reliably detect the novel coronavirus, SARS-CoV-2!

• Aerosol refers to solid or liquid particles that can remain suspended in the air. Their diameter can range from 0.003 micrometers to 100 micrometers. The coronavirus is transmitted mainly through respiratory droplets passed from person to person by coughing and close contact. However, transmission is also thought possible because of virus present in aerosols.
• Nanoparticles are structures ranging in size from a billionth to a ten-millionth of a meter. The term ‘Nanotanecik’ is also used in Turkish.

The idea of a biosensor for virus detection was not far removed from this research group's previous work. Even before COVID-19 began spreading first in China and then worldwide, Wang and his colleagues were researching sensors that could detect airborne bacteria and viruses. In early January, the idea arose of further developing a biosensor that could reliably identify a particular virus. Of course, the sensor will not replace existing laboratory tests, but it could serve as an alternative method for clinical diagnosis and simultaneously provide a clearer measurement of airborne virus concentrations, for example in crowded, busy places such as hospitals and railway stations.

Rapid and reliable tests are urgently needed to bring the global outbreak under control as quickly as possible. Most laboratories detect the virus in respiratory infections using a molecular method called reverse transcription polymerase chain reaction, or RT-PCR for short. This method is well established and can detect even very small amounts of virus, but it is time-consuming and may be prone to error.

An Optical Sensor for RNA Samples

Jing Wang and his team developed an alternative testing method in the form of an optical biosensor. The sensor combines two different effects to detect the virus reliably and safely: optical (light) and thermal (heat).

The sensor is based on tiny gold nanoparticles called gold nanoislands (AuNIs) on a glass substrate. Artificially produced DNA receptors matching the RNA sequences of SARS-CoV2 are grafted onto the nanoislands. The coronavirus is an RNA virus: its genome does not consist of the double-stranded DNA found in living organisms, but of single-stranded RNA. The receptors on the sensor are therefore complementary sequences that can reliably identify the virus's specific RNA strands.

The technology the researchers use for detection is LSPR (Localized Surface Plasmon Resonance). This is an optical phenomenon arising from these metallic nanoparticles: when excited, they modulate incoming light within a particular wavelength range and generate a plasmonic near-field around the nanoparticle. When molecules bind to the surface, the local refractive index within the excited plasmonic near-field changes. An optical sensor behind the sensor can be used to measure this change, determining whether the sample contains the RNA strand in question.

In the figure above, local LSPR responses scanned around the PPT heat source in AuNIs are shown. However, it is important that only RNA strands matching the DNA receptor exactly are present on the sensor. This is where a second effect on the sensor comes into play: the plasmolic photothermal (PPT) effect. If the nanoparticles on the sensor are excited by a laser at a specific wavelength, they generate localized heat.

Temperature Improves Reliability

How does this help reliability? As mentioned earlier, the viral genome contains a single RNA strand. If this strand finds its complementary partner, the two come together to form a double-stranded structure in a process called hybridization. The reverse – when the double strand separates into single strands – is called melting or denaturation. This occurs at a particular melting temperature. However, if the ambient temperature is lower than the melting temperature, non-complementary strands can also bind. If the ambient temperature is only slightly lower, only complementary strands join. This is the result of the increased ambient temperature caused by the PPT effect.

To demonstrate how reliably the new sensor detects the current coronavirus, the researchers tested it with a closely related virus: SARS-CoV. This is the virus that emerged in 2003 and triggered the global SARS outbreak. The two viruses (SARS-CoV and SARS-CoV2) differ only very slightly in their RNA. The validation was successful. Jing Wang explained, ‘The tests showed that the sensor can clearly distinguish between the very similar RNA sequences of these two viruses’. The results are also ready within a few minutes.

In the figure above, it is shown that very low viral concentrations can be measured using dual-functional LSPR biosensors. To assess detection performance, dual-functional plasmonic detection of RdRp-COVID was also investigated across a concentration range from 0.01 pM to 50 uM. In addition to the RdRp-COVID sequence, the dual-functional LSPR detection system was validated through selective hybridization detection in several different genomic sequences from SARS-CoV-2 and SARS-CoV: the ORF1ab-COVID sequence and E sequence from SARSCoV- 2, and the RdRp-SARS sequence from SARS-CoV.

Conclusion

Detecting environmental viruses with biosensors requires advanced bioengineering knowledge and experience. As this study shows, experience in biology, sensors and optics is being combined at scales of a billionth of a meter to produce sophisticated biotechnological devices. Products arising from this Zurich-based research could become major players in future global outbreaks. However, the sensor is not yet ready to measure airborne coronavirus concentrations, for example at Zurich's main railway station. A few further development steps are still needed, such as a system that draws in air, concentrates the aerosols it contains and releases RNA from the viruses. Wang says, ‘This still needs to be developed’. Once the sensor is ready, however, the principle could be applied to other viruses and help detect and stop an outbreak at an early stage.

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