Empa and ETH Zurich develop sensor for detection of COVID-19 virus

A team of researchers from Empa, ETH Zurich and the University Hospital Zurich has succeeded in developing a novel sensor for detecting the new coronavirus. In the future, it could be used to determine the virus concentration in the environment - for example, in places where many people are present or in hospital ventilation systems.

Especially at traffic junctions, the concentration of Covid-19 could be detected by the newly developed biosensor from Switzerland. (Image: Unsplash)

Jing Wang and his team at Empa and ETH Zurich usually work on measuring, analyzing and reducing air pollutants such as aerosols and man-made nanoparticles. But the current challenges facing the entire world are also changing the goals and strategies in research laboratories. The new focus: a sensor that can quickly and reliably detect SARS-CoV-2 - the new coronavirus.

However, the idea is not quite so far removed from the group's previous research work: Even before the COVID-19 virus began to spread, first in China and then around the world, Wang and his colleagues were researching sensors that can detect bacteria and viruses in the air. So back in January, the idea matured to use these fundamentals - and further develop the sensor to reliably identify a specific virus. The sensor is not necessarily intended to replace established laboratory tests, but it could be used as an alternative method for clinical diagnosis. And in particular, to measure the concentration of viruses in the air in real time, for example in busy places such as train stations or hospitals.

Rapid and reliable testing for COVID-19 is urgently needed to bring the pandemic under control as soon as possible. Most laboratories use a molecular method called reverse transcription polymerase chain reaction, or RT-PCR, to detect viruses in respiratory infections. This is established and can detect even tiny amounts of the viruses - but at the same time, the tests are often time-consuming.

An optical sensor for RNA samples
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The sensor uses an optical and a thermal effect to detect the COVID-19 virus safely and reliably.

Jing Wang and his team have developed an alternative test method in the form of an optical biosensor. The sensor combines two different effects to detect the virus safely and reliably: an optical and a thermal one.

The sensor is based on tiny structures of gold, so-called gold nanoislands, on a glass substrate. Artificially produced DNA sequences that match specific RNA sequences of the SARS-CoV-2 virus are applied to the nanoislands. The new coronavirus is a so-called RNA virus: its genome does not consist of DNA double strands, as in humans, animals and plants, but of a single RNA strand. The artificial DNA receptors on the sensor are therefore the complementary sequences to the unique RNA genome sequences of the virus, which can uniquely identify it.

The technology used by the researchers for virus detection is called LSPR ("localized surface plasmon resonance"). This is an optical phenomenon that occurs in metallic nanostructures: when excited, they modulate the incident light in a certain wavelength range and generate a so-called plasmonic near field around the nanostructure. When molecules dock onto the surface, the optical refractive index in this plasmonic near field changes at precisely this point. This can be measured with an optical sensor, which is located on the back of the sensor, and thus it can be determined whether the sought-after RNA strands are located in the sample.

Heat increases reliability

However, it is of course central that only those RNA strands are captured by the DNA receptor on the sensor that exactly match it. This is where a second effect comes into play: the plasmonic photothermal effect (PPT). When the same nanostructure on the sensor is excited with a laser of a specific wavelength, it produces heat.

So how does this help reliability? As already mentioned, the genetic material of the virus consists of only a single RNA strand. If this strand finds its complementary counterpart, the two combine to form a double strand - a process called hybridization. The opposite - when a double strand splits into single strands - is called melting or denaturation. This happens at a certain temperature, the melting temperature. However, if the ambient temperature is now much lower than the melting temperature, strands that are not 100% complementary to each other can also join. This can lead to incorrect test results. On the other hand, if the ambient temperature is only slightly lower than the melting temperature, only complementary strands can join. And this is exactly the result of the increased ambient temperature caused by the PPT effect.

To show how reliably the new sensor detects the current COVID-19 virus, the researchers tested it with a very closely related virus: SARS-CoV. This is the virus that triggered the SARS pandemic in 2003. The two viruses - SARS-CoV and SARS-CoV2 - differ only slightly in their RNA, making a clear distinction extremely difficult. But the experiment succeeded: "Our tests showed that the sensor can clearly distinguish between the very similar RNA sequences of the two viruses," explains Jing Wang.

At the moment, the sensor is not yet ready to measure the concentration of coronaviruses in the air at Zurich's main train station, for example. A few steps are still needed for that - such as a system that sucks in the air, concentrates the aerosols in it and isolates the RNA from the viruses. "That still needs development work," Wang says. But once the sensor is completed, the principle could be applied to other viruses - and help detect and perhaps even stop future epidemics early. (Source: Empa)

Literature:

G Qiu, Z Gai, Y Tao, J Schmitt, G A Kullak-Ublick, J WangDual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection; ACS Nano 2020, doi.org/10.1021/acsnano.0c02439

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