Sorting out viruses with machine learning

Single virus particle detections using a solid-state nanopore
Credit: Osaka University

Scientists at Osaka University develop a label-free method for identifying respiratory viruses based on changes in electrical current when they pass through silicon nanopores, which may lead to new rapid COVID-19 tests.

The ongoing global pandemic has created an urgent need for rapid tests that can diagnose the presence of the SARS-CoV-2 virus, the pathogen that causes COVID-19, and distinguish it from other respiratory viruses. Now, researchers from Japan have demonstrated a new system for single-virion identification of common respiratory pathogens using a machine learning algorithm trained on changes in current across silicon nanopores. This work may lead to fast and accurate screening tests for diseases like COVID-19 and influenza.

In a study published this month in ACS Sensors scientists at Osaka University have introduced a new system using silicon nanopores sensitive enough to detect even a single virus particle when coupled with a machine learning algorithm.

In this method, a silicon nitride layer just 50 nm thick suspended on a silicon wafer has tiny nanopores added, which are themselves only 300 nm in diameter. When a voltage difference is applied to the solution on either side of the wafer, ions travel through the nanopores in a process called electrophoresis.

The motion of the ions can be monitored by the current they generate, and when a viral particle enters a nanopore, it blocks some of the ions from passing through, leading to a transient dip in current. Each dip reflects the physical properties of the particle, such as volume, surface charge, and shape, so they can be used to identify the kind of virus.

The natural variation in the physical properties of virus particles had previously hindered implementation of this approach, however, using machine learning, the team built a classification algorithm trained with signals from known viruses to determine the identity of new samples. “By combining single-particle nanopore sensing with artificial intelligence, we were able to achieve highly accurate identification of multiple viral species,” explains senior author Makusu Tsutsui.

The computer can discriminate the differences in electrical current waveforms that cannot be identified by human eyes, which enables highly accurate virus classification. In addition to coronavirus, the system was tested with similar pathogens – respiratory syncytial virus, adenovirus, influenza A, and influenza B.

The team believes that coronaviruses are especially well suited for this technique since their spiky outer proteins may even allow different strains to be classified separately. “This work will help with the development of a virus test kit that outperforms conventional viral inspection methods,” says last author Tomoji Kawai.

Compared with other rapid viral tests like polymerase chain reaction or antibody-based screens, the new method is much faster and does not require costly reagents, which may lead to improved diagnostic tests for emerging viral particles that cause infectious diseases such as COVID-19.

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The article, “Digital pathology platform for respiratory tract infection diagnosis via multiplex single-particle detections,” was published in ACS Sensors at DOI: https://doi.org/10.1021/acssensors.0c01564

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan’s leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan’s most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en/top

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Saori Obayashi
Osaka University

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