Fighting Covid-19 with Light

Whether it is reliable sterilization, fast diagnoses, or research to gain a deeper understanding of infections, photonics supports the battle against the pandemic on many fronts.

UV-C light in the wavelengths range around 250 nanometers reliably kills the SARS-CoV-2 virus. The mechanism of action is that in the virus nuclei the chemical element thymine absorbs the UV-C waves which kills the virus and prevents it from propagating. There are now several UV-C light sources available. Osram supplies Chinese hospitals which use it to sterilize surfaces. LASER COMPONENTS offers LED-based UV-C systems. And in Berlin, Germany, the Ferdinand-Braun-Institut, Leibniz-Institut für Höchstfrequenztechnik (FBH) has developed an LED array system that emits UV-C light with 230 nanometers wavelength to kill viruses. The first robots for automated UV-C sterilization are also on the market.

Due to the intensive UV-C radiation, surface sterilization can take place only in rooms where no people are present. But the FBH, together with medical research institutions, is investigating whether small doses of UV-C radiation could also be suitable to fight viruses on mucous membranes in the nasal cavity and pharynx. It has to be clarified whether, in addition to killing viruses, the short-wave light also damages the genetic material of the radiated body cells.

Quick diagnosis with light

The key to containing the pandemic is early detection of infections. Imaging systems based on high-resolution thermal imaging cameras can help by recognizing people who are potentially infected on the basis of their raised body temperature. Modern systems are able to capture the body temperatures of several people at the same time. These contactless and, thanks to modern infrared lenses, high-resolution systems focus on the inner canthus between the eye and nose and measure with a level of accuracy to a tenth of a degree. The use of mobile measuring stations is also conceivable. STEMMER IMAGING is one of the companies offering a modular system based on a longwave infrared (LWIR) camera that can be assembled in minutes and could be interesting for large events.

Body temperature screenings are a first step. But a practical detailed diagnosis is needed to clarify whether the fever is actually due to the SARS-CoV-2 virus. Here, too, photonics offers new solution approaches, such as analysis of infected cells using Raman microscopy. This is based on the principle that photons inserted in samples via laser interact with bio-molecules. Their energy level falls, which produces a scattering spectrum that is characteristic for the respective molecule. Implemented in a highly sensitive Raman trapping microscope, the principle can be used for Covid-19 diagnosis; especially as investigated body cells can be fixed in the laser focus with optical tweezers for Raman analysis. Combined with a GigE color camera from Allied Vision, the system enables fast, semi-automated analyses. According to the manufacturer, CellTool, comparison tests with common, much more complicated test methods confirm the findings of the Raman-based virus detection.

An innovative sensor

Scientists at the Leibniz Institute for Analytical Sciences—ISAS and TU Dortmund University have also developed an optical sensor system for rapid detection of the SARS-CoV-2 virus. It makes the 100 to 140 nanometer small viruses visible within minutes via the indirect method of surface plasmon resonance. To do this, a gold-coated prism is radiated with a laser. The extremely fine gold layer is coated with specific antibodies. If a saliva or wastewater sample contains SARS-Cov-2 viruses, they bond to the antibodies, which measurably changes the plasmon resonance. The plasmon waves scattered on the virus are analyzed with a camera-based imaging system that evaluates the signals in real time using artificial intelligence. The physicists, computer scientists, and mathematicians at TU Dortmund University have proved the effectiveness of their PAMONO sensor on various viruses, including HIV and hepatitis. Pharmaceutical producers are already using the method in quality controls. The ISAS team is now pushing ahead to develop a rapid test for corona. For safety reasons, they are using enucleated but fully intact virus-like particles (VLP)

Scientists around the world are looking for optical high-throughput methods. Some are investigating time and spatial ultra-high-resolution fluorescence microscopy to get a deeper understanding of the viruses and the function of their proteins. Others are using widefield fluorescence microscopes in combination with imaging technologies and machine learning to detect SARS-Cov-2-specific antigens in human blood serums. This is precisely what an international team associated with the Infectious Diseases Imaging Platform of Heidelberg University in Germany investigated in a recent study involving more than 5,000 volunteers. According to the European network Euro-Bioimaging, the pre-published results show that the sensitivity and specificity of COVID-19 diagnosis using high-throughput microscopy with automated evaluation are superior to the approved ELISA-based diagnoses. The experts especially emphasize that the methods detect all viral antigens of SARS-CoV-2-infected cells, while ELISA methods detect only one or a few selected antigens. Since patients develop different spectra of antibodies, the new microscopic detection method lowers the risk

Microscopic foray into the nano range

While fluorescence microscopy seems to be suitable for the rapid detection of viruses, it cannot be used to observe the infection and propagation process on a cell level. On the one hand, the dyes that are used bleach within seconds and are often toxic, which makes it difficult to use them in living cell cultures. On the other hand, the sensitivity and resolution are not sufficient to spatially capture the nanoscopic movements of the 100 nanometer small viruses in infected cells. However, according to Professor Vahid Sandoghdar, director at the Max Planck Institute for the Science of Light in Erlangen and head of the department for experimental physics at the University of Erlangen-Nuremberg, this would be important to get a better understanding of the infection process in the cells. “How long does it take until viruses enter human cells where they propagate and how long until a new virus generation infests other cells?” he asks. A joint research project with the Virology Institute at University Hospital Erlangen could provide the answers. The focus is on the new microscopy method developed by Sandoghdar and his team, which makes use of the interferometric scattering (iSCAT) of nanometer small bio-molecules. With this method the team now also makes SARS-CoV-2 viruses visible by evaluating the interference pattern of the laser light scattered on them.

The goal is to achieve minute or even hour-long live streams from infected cell cultures. After having miniaturized an iSCAT microscope for use in the high-security laboratory, the team is now looking at complex virus detection in cell cultures. “The difficulty is that the other bio-molecules also scatter in the cells,” explains Sandoghdar. However, his team is working on the task of identifying the interference pattern of the viruses step by step. The scientists begin with simple analyses, such as quantifying viruses in samples or specifically adding viruses to cells that have already been observed, to track local changes in the interference pattern. In this way, the scientists are laying the foundations for their microscopic foray into the nano range—and, according to Sandoghdar, are backing up their observations with supporting fluorescence microscopy. As is often the case, once again it is photonics that is paving the way for new photonic methods.

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