Nanopore sensors for breath-based disease detection
Scientists at the University of Oxford, led by Professors Yujia Qing and Hagan Bayley FRS, have developed a simple sensor that can detect molecules known as volatile organic compounds (VOCs), many of which are diagnostic of life-threatening medical conditions.
Published today in Nature Communications, the technology uses reversible chemistry inside a protein nanopore to distinguish between near-identical VOCs, offering a route to fast, low-cost diagnostic testing.
Our breath and body fluids contain thousands of VOCs; both their composition and relative levels shift with illness, providing a non-invasive window into health. These changes have been associated with diseases including cancer, infections, and respiratory or metabolic disorders.
Detecting these subtle changes typically requires chromatography-coupled mass spectrometry, a powerful but complex technology that involves large, expensive machines run by trained specialists. Researchers from Oxford Chemistry have developed a simpler approach based on nanopore sensing technology, which measures ionic current changes as molecules pass through a protein pore. The same principle underpins nanopore sequencing, which is now deployed in portable devices around the world that have revolutionised genomics and epigenomics.
In this new study, the Oxford team focused on aldehydes, an important class of small molecules associated with conditions such as lung cancer and viral infections like COVID-19. Around 170 different aldehydes are found in human breath, making them a rich source of potential biomarkers.
The sensor identifies individual aldehyde molecules as they pass through the pore, where they undergo a brief, reversible reaction that generates a unique signal for each compound. This even enables the discrimination between aldehyde isomers, which share the same chemical formula but differ in 3D structure, a task that often proves difficult for traditional detection methods.
Furthermore, the team identified a way to spot alcohols, another key class of disease-related molecules. Because alcohols do not react directly in the pore, they were first converted into aldehydes with an enzyme, showing the platform’s ability to identify a broad range of biomarkers by leveraging simple sensing chemistry.
The approach is compatible with low-cost, portable, user-friendly devices for use in clinics or even at home. Portable DNA/RNA sequencers based on nanopore sensing are already widely used in the field and in clinical research, and this study points to new opportunities to apply the technology in chemical and disease diagnostics. The sensors could also be used for environmental monitoring, ensuring food and beverage quality, and supporting quality control of pharmaceuticals. By combining simple ionic current readouts with careful sensor engineering, the study points to a future where advanced chemical sensing is accessible in everyday settings.
This work was supported by the Bill and Melinda Gates Foundation.
Summary by Fay Green, a DPhil student in the Qing group.
