Researchers have introduced LUCAS (Luminescence Cascade-Based Sensor), a next-generation bioluminescent immunoassay capable of rapidly detecting viruses such as SARS-CoV-2, HIV, HBV, and HCV with exceptional sensitivity. Their work, recently published in Nature Biomedical Engineering, outlines a portable diagnostic tool that combines enzyme chemistry with smartphone integration to deliver accurate results in under 23 minutes.
Study: Ultrasensitive and long-lasting bioluminescence immunoassay for point-of-care viral antigen detection. Image Credit: Gorodenkoff/Shutterstock.com
Rethinking Bioluminescent Detection
Bioluminescent assays have long offered theoretical advantages for diagnostics. They generate strong signals without requiring external light sources, which helps minimize background interference. Yet in practice, traditional systems built on luciferase enzymes fall short, mainly because the light signal fades quickly, and enzyme activity tends to drop when linked to antibodies used for targeting.
These limitations are particularly problematic when testing complex biological samples, where weak or short-lived signals can lead to missed infections. Attempts to improve performance using synthetic enzymes or fragments have seen limited success, often trading stability for activity. Meanwhile, rapid tests like lateral flow assays offer speed and simplicity but lack the sensitivity to detect low viral loads, making them less useful for early-stage detection or precise monitoring.
Motivated by these challenges, and by the diagnostic demands highlighted during the COVID-19 pandemic, the research team set out to engineer a system that maintains bioluminescent benefits while eliminating its key drawbacks. Their solution is an enzyme cascade designed to both amplify the signal and extend its duration.
Inside the LUCAS System
At the core of LUCAS is a multi-step biochemical reaction that produces a significantly stronger and more stable light signal than conventional bioluminescent assays. The process begins with magnetic beads coated in capture antibodies, which bind to viruses present in patient samples such as serum or nasal swabs.
Once the virus is isolated, a second antibody, tagged with the enzyme β-galactosidase (GAL), attaches to the viral antigen. When a specific substrate is added, GAL converts it into a luciferin precursor. This precursor is then transformed by firefly luciferase (Fluc) into visible light.
What sets this cascade apart is its ability to amplify the final signal while also prolonging its visibility. In contrast to conventional systems, where luminescence fades within minutes, LUCAS maintains a readable signal for over an hour, giving users a much wider and more forgiving time window for detection.
To make the assay practical for non-laboratory environments, the researchers developed a portable device that automates the entire process. It handles sample mixing, reagent delivery, incubation, washing, and signal detection, all coordinated through a smartphone app. A manual version was also created for early validation before transitioning to full automation.
Performance and Practicality
The system delivered an impressive 500-fold increase in signal intensity compared to traditional approaches, with the added benefit of long-lasting stability. It consistently detected viral loads as low as 119 copies per milliliter, which is especially valuable for identifying infections at early stages.
Clinical testing showed that LUCAS could accurately classify infected versus uninfected samples with over 94 % accuracy across a range of viruses. Importantly, the assay maintained strong specificity, avoiding cross-reactions between different pathogens.
The entire testing cycle takes less than 23 minutes from sample to result. The user-friendly design, combined with the absence of a need for external power or specialized training, makes the system ideal for use in clinics, remote areas, and other low-resource settings.
Why it Matters
What makes LUCAS notable isn’t just its sensitivity—it’s the combination of speed, simplicity, and reliability in one integrated platform. The enzyme cascade not only strengthens the light signal but also makes the assay more resilient to environmental variables, like temperature changes or inconsistent timing. This expands its usefulness outside the controlled conditions of a lab.
By packaging the assay into an automated, portable device, the researchers have made advanced viral detection accessible to a much broader range of users. And because the platform can be adapted to recognize multiple viruses, it offers a flexible foundation for future diagnostics, particularly during outbreaks where quick, accurate responses are crucial.
Conclusion
The LUCAS system represents a significant step forward in point-of-care diagnostics. By addressing the core limitations of traditional bioluminescent assays—rapid signal decay and fragile enzyme activity—it delivers reliable, high-sensitivity viral detection in a compact, easy-to-use format. With its ability to detect multiple pathogens and operate without external infrastructure, it holds strong potential for real-world impact in both clinical and resource-limited settings.
Journal Reference
Kim S., Cho G., et al. (2025). Ultrasensitive and long-lasting bioluminescence immunoassay for point-of-care viral antigen detection. Nature Biomedical Engineering. DOI: 10.1038/s41551-025-01405-9, https://www.nature.com/articles/s41551-025-01405-9