IISc Researchers Innovate Paper-Based Sensor for Early Liver Cancer Detection

Researchers at the Indian Institute of Science (IISc) have pioneered a groundbreaking luminescent probe utilizing terbium, a rare earth metal, to detect the enzyme β-glucuronidase, which serves as a crucial biomarker for liver cancer. This innovative development, which culminates nearly a decade of research, provides a simple, cost-effective paper-based sensor that could revolutionize early cancer detection in resource-limited settings.

The enzyme β-glucuronidase is an evolutionarily conserved component found across different life forms, from microbes to plants and animals. Its primary function is to break down glucuronic acid, but its elevated levels have been linked to various cancers, including liver, colon, breast, and renal cancers, as well as infections such as urinary tract infections and AIDS. This makes it an important target for cancer diagnostics.

Conventional detection methods, including colorimetry and fluorescence, often suffer from low sensitivity and interference from background signals. Ananya Biswas, a former PhD student at IISc and co-first author of the study published in Chemistry, explained, "The ability of rare earth metals to have long-lived excited states allows us to filter out short-lived background fluorescence, resulting in a much clearer signal."

The genesis of this project traces back to experiments conducted by the research team on the gel-forming properties of metal ions. They discovered that terbium ions embedded in a gel matrix derived from bile salts exhibited green fluorescence. To enhance the detection capability, the team incorporated an organic molecule known as 2,3-DHN (2,3-Dihydroxynaphthalene) masked with glucuronic acid within the same gel matrix. Upon exposure to β-glucuronidase, the enzyme cleaves the modified molecule, leading to the release of free 2,3-DHN.

Uday Maitra, an honorary professor in the Department of Organic Chemistry at IISc and corresponding author of the study, noted, "The free 2,3-DHN acts as an 'antenna'—absorbing UV light and transferring energy to the nearby terbium ions, significantly enhancing their green emission. The gel matrix ensures sufficient proximity between the 'antenna' and terbium ions, facilitating efficient energy transfer."

For practical application, the researchers have designed a user-friendly paper-based sensor by anchoring the gel matrix onto a paper disc. When β-glucuronidase pre-treated with the modified 2,3-DHN is applied, the disc emits a significantly stronger green glow under UV light. This innovative technique stands out due to its ease of analysis; unlike traditional high-end fluorescence detection systems, this paper-based sensor can be analyzed using a UV lamp and ImageJ, an open-source software. This makes the technology particularly suitable for use in resource-limited settings, providing a potentially transformative tool for early cancer detection.

The implications of this research extend beyond liver cancer detection; the methodology could be adapted for other types of cancer and diseases where β-glucuronidase levels are elevated. As Uday Maitra stated, "Our work opens avenues for the development of accessible diagnostic tools that can significantly enhance healthcare outcomes, especially in underserved populations."

With the growing burden of cancer globally, particularly in developing nations, innovations such as this paper-based sensor are critical. The researchers at IISc aim to further refine the technology and explore its application in various clinical settings, paving the way for enhanced diagnostic capabilities that could save lives through early intervention. The study was published on June 30, 2025, underscoring the ongoing commitment of IISc to advance medical technology for social benefit.