Indian Scientists Develop Easy And Low-Cost Method To Detect Liver Cancer Using A Paper-Based Sensor
Indian researchers developed a low-cost paper-based terbium sensor to detect β-glucuronidase, a biomarker linked to liver cancer and other diseases.
By Anubha Jain
Published : July 11, 2025 at 4:08 PM IST
Bengaluru: Scientists at the Indian Institute of Science (IISc) have developed an innovative, affordable sensor that can easily detect the enzyme β-glucuronidase—one of the biomarkers for liver cancer. Our body connects glucuronic acid (a sugar-acid) to many harmful compounds for their easy removal (detoxification). However, this enzyme—found across many living organisms—can remove the sugar, thereby releasing the toxic compounds, some of which can cause cancer.
Elevated β-glucuronidase levels are linked not only to liver cancer but also to breast, colon, prostate, and kidney cancers, urinary infections, and AIDS.
To develop the diagnostic tool to detect this enzyme, the IISc researchers used terbium—a rare earth lanthanide metal known for its sharp green luminescence. The team created a gel-based matrix containing terbium ions, which glows green under ultraviolet (UV) light.
They incorporated a compound, 2,3-DHN, which was chemically "masked" with glucuronic acid, in the gel. In the presence of β-glucuronidase, this sugar mask gets detached, releasing free 2,3-DHN, which then acts as an antenna, absorbing UV light and transferring the energy to terbium ions. This results in a bright green emission.
“Conventional colourimetric and fluorescence-based techniques often struggle with sensitivity and interference from background signals. Lanthanide metals like terbium have long-lived excited states, allowing for time-resolved detection and reducing signal noise,” explained Ananya Biswas, former PhD student at IISc and co-author of the study.
The Journey from Curiosity to Clinical Potential
Initially studying how bile salts and calcium form gels, the scientists discovered that replacing calcium with lanthanide ions, including terbium, led to unique metallogels. In the bile salt gels, these ions exhibited photoluminescence when the gels were doped with suitable antenna molecules like 2,3-DHN.
This research effort has roots stretching back over a decade when the team began exploring metal ion-based gel formation. In an exclusive interview with ETV Bharat, Uday Maitra, the study’s lead author and honorary professor at IISc’s Department of Organic Chemistry, discussed the discovery in detail.
Talking about exploring terbium and bile salt gels for enzyme detection, Maitra said, "Lanthanide ions don’t naturally emit strongly in water due to quenching by water’s O–H vibrations, and because of their low light absorbing power. But by embedding them in hydrophobic gels and adding antenna molecules, we can shield them from water and enhance their light emission.”
Bile salts, derived from cholesterol in the liver, aid in the digestion of fats. In 2010, the scientists found that mixing bile salts with a variety of metal ions formed gel-like materials. Later, they discovered that rare-earth metals could also form similar gels. When lanthanide ions were combined with special light-absorbing molecules called antennas, the gel began to glow under light. The antenna didn’t need to be chemically attached—it just needed to be located in close proximity.
Scientists then made the antenna “inactive” until a specific enzyme “unlocked” it, switching the glow on. This idea was first tested with the lipase enzyme in 2012. Since then, it has been expanded to detect other enzymes linked to diseases, making it a useful and low-cost tool for health and environmental monitoring.
Transforming to a Paper-Based Format
When asked about 2,3-DHN, why it was chosen as the ‘antenna’ molecule, and how its chemistry complements terbium ions, Maitra explained that for energy transfer to be effective, the antenna molecule must have an excited-state energy level higher than that of the lanthanide ion. This allows the antenna to absorb light and pass the energy to the lanthanide, which then emits light through its unique electronic transitions. The team was fortunate to achieve success with their very first system using terbium(III) ions. The selected antenna had the ideal photophysical properties—particularly a triplet energy level well matched to terbium’s emission level—leading to efficient energy transfer and bright green luminescence.
This initial success validated their design strategy and provided a solid foundation for future work. The sensor's performance was further enhanced by a bile salt-based gel matrix, which forms through self-assembly when just 1 per cent by weight of bile salts and metal ions are used. The resulting fibrous, thread-like network is formed via non-covalent interactions like hydrophobic forces and metal coordination. Within this gel, the antenna molecules naturally attach to the fibres rather than staying in solution.
This spatial proximity to the embedded lanthanide ions enables effective energy transfer. According to Professor Maitra, the working model involves a three-part self-assembly of bile salt, the lanthanide ion, and the antenna, creating a nano-fibrous structure that supports robust photoluminescence.
While discussing the significant hurdles in designing the paper-based format, especially in maintaining the structural integrity and fluorescence efficiency, he said, “Using a trial-and-error method, the team developed a simple, low-cost paper-based sensor. They coated filter paper with the gel (98 per cent water), which dried into a xerogel. Initially unsure if it would retain its luminescent and reactive properties, microscopy confirmed that the fibrous gel network bonded well with the paper. Maintaining slight moisture was key, and surprisingly, the paper format often showed better sensitivity than the original hydrogel.
Sensor's User-Friendliness
To make this sensor easy to use, the researchers coated the gel on paper discs. When exposed to samples containing the enzyme, the paper glows more brightly under UV light. This paper sensor provides a user-friendly solution:
- Add a biological sample
- Wait briefly
- Observe any change under a simple UV lamp
The low-cost liver cancer detection technique uses a luminescent sensor, and the results can be analysed using open-source software like ImageJ, eliminating the need for expensive lab equipment. To improve reaction kinetics, a premixed gel can also be coated onto paper before testing. The process is simple and doesn’t require any technical expertise.
On clinical validation, he mentioned that collaborations are being discussed, but real-world testing is pending. Once validated with patient samples, the sensor could have practical applications.
Adaptability of the IISc sensor
As mentioned earlier, β-glucuronidase is also linked to other cancers and conditions. Discussing how adaptable is IISc sensor is for broader clinical diagnostics beyond liver cancer, the professor said that glucuronidation plays a key role in detoxification by connecting harmful compounds to glucuronic acid, making them water-soluble for excretion. However, elevated levels of this enzyme can reverse the process, regenerating toxic forms and causing cellular stress. While not a standalone diagnostic tool, it can signal the need for further tests. Large-scale validation is still needed to confirm its clinical reliability and specificity.
The sensor developed at IISc has a Limit of Detection (LOD) of 185 ng/mL for β-glucuronidase, an enzyme elevated (∼1,000 ng/mL) in advanced liver disease like decompensated cirrhosis, matching the sensitivity of standard diagnostic assays. Its use of lanthanide-based photoluminescence—known for sharp emission peaks and long lifetimes—minimises background interference, enabling clear, high-sensitivity detection even in complex biological samples.
Lanthanide ions, such as terbium or europium, exhibit long emission lifetimes and sharp, well-resolved emission bands, which significantly reduce background interference from biological autofluorescence. This allows for time-gated luminescence measurements, enhancing the signal-to-noise ratio and enabling high-sensitivity detection of β-glucuronidase activity in complex biological matrices.
Next Steps: Optimisation and Commercialisation
To enable wider use of the sensor, IISc researchers developed a molecular blocker that controls energy transfer to the lanthanide ion, activating the sensor only in the presence of β-glucuronidase. Initially synthesised using low-cost, readily available materials, the blocker now requires optimisation for better yield and scalability.
Upcoming milestones include enhancing the sensor’s sensitivity and portability while reducing dependence on costly equipment like microplate readers. The goal is to create a miniaturised, low-cost diagnostic tool without compromising accuracy.
Clinical validation is the final critical step to confirm the sensor’s reliability in real-world settings. Given β-glucuronidase’s link to liver and other cancers, neonatal jaundice, and drug toxicity, this technique holds strong promise for affordable, point-of-care diagnostics in resource-limited environments.
