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New principle for antibody tests: Thomas Mortelmans receives the Swiss Nanotechnology PhD Award

Dr. Thomas Mortelmans, a former doctoral student at the SNI PhD School, was presented with one of five PhD Awards at the Swiss NanoConvention 2022. He received the award, which is sponsored by Sensirion, in recognition of a first-author publication in the journal ACS Applied Nanomaterials in which Mortelmans described a novel functional principle for rapid Covid-19 tests. The principle can also be used to determine the status of the disease or to detect other viruses, such as influenza A.

In recent years, almost all of us have taken numerous rapid tests to find out whether we’re infected with SARS-CoV-2. The rapid antigen tests available on the market are not always reliable, however, and sometimes fail to return a positive result even with a high viral load — as demonstrated by a study from the Paul-Ehrlich-Institut (PEI) in Germany. Furthermore, these tests only ever give us a yes/no answer without providing information about the status of a disease or its progression.

The test developed by Thomas Mortelmans as part of his doctoral dissertation at the SNI PhD School is based on a different principle. It detects not only specific virus components but also antibodies produced by the human immune system in response to an infection with the virus. As the antibodies change over the course of an infection and as the number of them varies depending on disease progression, the test delivers other useful information. Moreover, the test principle developed by Mortelmans can also be used to detect antibodies against other diseases.

Sensitive and straightforward to carry out
“The test could theoretically be carried out at medical practices using a straightforward technique,” explains Mortelmans. “All it needs is a drop of the patient’s blood. This sample is then mixed with a specially prepared liquid that contains not only nanoparticles with surfaces closely resembling those of coronaviruses, but also fluorescent particles that selectively bind to the antibodies from the patient.”

If the blood sample contains antibodies specific to Covid-19, these will recognize the similar surface on top of the nanoparticles and bind to it. This adherence is visualized with the help of the fluorescent particles, which will specifically bind to the patient’s antibodies.

Once processed in this way, the blood sample is dripped onto a Plexiglas plate that has been etched with a sophisticated pattern of nanochannels. There are several very narrow points along the course of these channels, which produce a strong capillary effect thanks to their specially developed shape. This effect draws the sample from the start to the end of the channel with no need for technical assistance. “As the antibody–nanoparticle aggregates pass through the nanochannels, they get stuck at particularly narrow points,” explains Mortelmans. “The fluorescent appendages would allow physicians to observe this effect under a microscope and therefore to detect an infection with a high degree of sensitivity.”

“Based on the signal strength, it’s also possible to identify whether the immune system is responding effectively and whether the disease is likely to be mild or severe,” adds Dr. Yasin Ekinci, head of the Laboratory for X-ray Nanoscience and Technologies at the Paul Scherrer Institute PSI, who was one of the project leaders.

Applicable to other tests
With this test principle, nanoparticles of a different size can also be added in order to bind to different antibodies. “These nanoparticles then get ‘stuck’ at a different point in the capillary, allowing us to detect a different disease using the same sample,” says Mortelmans. In the prizewinning publication in ACS Applied Nanomaterials, he used influenza A viruses to demonstrate that the tests can be combined in this way.

Despite the positive results, further development of the system into a coronavirus test looks set to be discontinued due to a lack of reimbursement from health insurance funds. “With our work, however, the key thing is that we were able to prove that these kinds of tests can be used to detect various diseases. You could easily test for ten different diseases at the same time, detecting them quickly and reliably using different colors,” explains Mortelmans.

Originally intended for mitochondria
When Mortelmans began his dissertation at the SNI PhD School in 2018, the focus was not initially on detecting SARS-CoV-2. Rather, the two project leaders Dr. Yasin Ekinci (PSI) and Professor Henning Stahlberg (then of the University of Basel; now at EPFL) had submitted a project proposal within the framework of the SNI PhD School for the development of a microfluidic diagnostic method for Parkinson’s disease. The technique involved quantifying and determining the size of mitochondria, as the neurodegenerative disease is closely linked to the size and number of mitochondria in affected cells.

At about the same time, Mortelmans was in Belgium looking for a position as a doctoral student in the field of biomedicine. “I’d just completed my master’s thesis at Hasselt University (Belgium) and was open to a new challenge,” he recalls. “When I looked online for an interdisciplinary doctoral dissertation, the project at the SNI PhD School appeared right at the top of the list,” he adds. “I was immediately drawn by the description, so I applied and quickly received an offer.”

During this work, the test system was subsequently geared toward SARS-CoV-2 in early 2020, at which point Hennig Stahlberg had left the University of Basel and news of the first coronavirus cases had arrived from China. “Although I lost a couple of months as a result, it was very exciting to be working on such a topical issue,” says Mortelmans.

Next step: the pharmaceutical industry
In July 2022, Mortelmans went on to receive the Swiss Nanotechnology PhD Award, which is sponsored by the company Sensirion, for the publication in which he, as first author, described the test system. He also completed his dissertation at about the same time, earning a top grade. Since September 2022, Mortelmans has been working as a trainee at Johnson & Johnson in Schaffhausen, where he’s currently familiarizing himself with the various divisions of the global pharmaceutical company.

In his current role as a StepIn Trainee, he will undergo three rotations in various departments of the J&J site in Schaffhausen. Currently, he is assisting the Operational Support team of the Optical Inspection, Device Assembly and Packaging branch in various tasks, ranging from data analysis, to risk assessment and project development. The rotational program exposes Thomas to a lot of new technology and methodologies. “This requires that you are comfortable in communicating with people with different educational background. This is quite similar to being a PhD student at the SNI, where you are building the bridge between different scientific disciplines in the framework of an interdisciplinary project”, he reports.

Great time
Looking back, Mortelmans had a tremendous time at the Paul Scherrer Institute and the SNI PhD School. “I really enjoyed the interdisciplinary collaboration. Events such as the Winter School and the SNI Annual Event were real highlights and taught me a lot about different subject areas. Today, these insights allow me to consider problems from various angles,” he says. What’s more, it was no problem for him to belong to two institutions and two working groups at PSI and the University of Basel — actually, it turned out to be an asset.

Further information:

Media release about the publication in ACS Applied Nanomaterials
Video about the publication
Publikation in ACS Applied Nanomaterials
Video with Thomas Mortelmans about the SNI PhD School