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‘Coronascope’ enables live observations of COVID-19 infections

virus infected cell
A human cell (HeLa) infected with vaccinia viruses in an image produced by an iScat microscope. The arrows point to single viruses. (Image: MPI for the Science of Light)

Max Planck Centre for Physics and Medicine develops video monitoring in high-security virology lab.

A type of video monitoring could help us get the better of coronavirus: Researchers at the Max Planck Institute for the Physics of Light and FAU are trying to observe how cells become infected with Sars-CoV-2 in real time. They are hoping to achieve this by installing a particularly powerful microscope in a high-security virology laboratory.

The iScat imaging process enables the scientists in Erlangen to observe the interaction of live viruses and cells over a longer period of time with high spatiotemporal resolution. The cooperation within the Max Planck Centre for Physics and Medicine could also help develop therapies to treat COVID-19.

An infection is a race against time and the coronavirus pandemic is making it all too clear that it is often a matter of life and death. On a large scale, this involves the efforts to slow the spread of the COVID-19 pandemic and on a small scale, it applies to the immune system of an infected patient as it attempts to gain the upper hand over the virus. The illness takes hold when the virus multiplies immediately after infection at a rate faster than the body can fight it.

‘An important factor in this race is how long it takes until a virus penetrates a human cell, multiplies and then releases the new generation of the virus, which in turn infects more cells,’ explains Vahid Sandoghdar, Director of the Max Planck Institute for the Science of Light in Erlangen and head of one of the Chairs of Experimental Physics at FAU. ‘We currently don’t know in detail what happens during each single step on the cellular level or in cell tissue.’

Sandoghdar’s team therefore wants to perform live observations of the propagation cycle of the virus in conjunction with a team led by Klaus Überla, Director of the Institute of Clinical and Molecular Virology at Universitätsklinikum Erlangen and Chair of Clinical and Molecular Virology. ‘I am looking forward to working on this interesting project,’ says the virologist. The medical specialists and physicists also want to observe how potential candidates for medical substances influence cell-virus interaction and multiplication directly on a single cell.

Three weeks required to build an iScat microscope

The researchers can now film the processes at cellular level using an iScat microscope. iScat stands for interferometric scattering. The instrument maps tiny structures such as the coronavirus, which is around 100 nanometers in size, using sophisticated analysis of interference patterns that are generated when light is scattered on the particles. With his team, Vahid Sandoghdar has developed this technique during the last few years and has now perfected it to such an extent that it is now possible to make nanofilms of biological processes.

The group has now built an iScat microscope or ‘Coronascope’, as it’s known by Sandoghdar, during the course of only three weeks for use in a BSL3 (biosafety level 3) laboratory. Such high-security laboratories have several precautions in place to prevent infection with pathogens. Space for equipment is limited and there are strict rules about entering the laboratory.

The Max-Planck team therefore reduced the size of its apparatus including the optical instruments from something larger than a dining table to a steel box no bigger than a microwave. The researchers also modified the instrument so that it can now be operated and maintained remotely. ‘This involved a great deal of engineering work,’ says Sandoghdar. ‘Our team worked extremely hard.’

First images available in a few days

The hard work will pay off, as iScat has a few advantages compared to other methods of imaging viruses. In contrast to electron microscopes, it can produce images of living viruses and even film biological processes. There is no need to label the viruses with fluorescent proteins as is the case with fluorescence microscopy. The fluorescent markers fade relatively quickly and too quickly to enable the entire propagation cycle to be captured. ‘Quite apart from this fact, there is no practical solution available at short notice for marking the new coronavirus with fluorescent proteins,’ says Vahid Sandoghdar.

Since it was not possible to observe the propagation cycle in this way in the past, virologists had to determine the rate of multiplication simply by measuring how many viruses form in a cell culture during a specific period of time. ‘We can now supplement these measurements with insights on the cellular level,’ says Sandoghdar. The researchers are hoping to take the first images with the Coronascope in a few days’ time.

Max Planck Centre for Physics and Medicine

The collaborative research carried out on Sars-CoV-2 is an example of the work carried out by the Max Planck Centre for Physics and Medicine. At the centre, researchers at the Max Planck Institute for the Science of Light, FAU and Universitätsklinikum Erlangen use physical effects in order to gain new medical findings. With this new microscopic video monitoring of the coronavirus, they not only hope to increase their understanding of the infection, but also to gain new approaches for treatments.

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