Ultrasensitive Luminescence-based Yeast Sensor for Specific Early cancer Sensing

ULYSSES is a pioneering project aimed at developing a non-invasive, portable, and user-friendly biosensor for the early detection of breast and prostate cancers through urine analysis.

Its core vision is to identify cancer-related volatile organic compounds (VOCs) and develop a biotechnological device for their detection in urine. The innovation lies in mimicking the extraordinary olfactory system of the nematode Caenorhabditis elegans, which can distinguish cancerous from healthy urine with over 90% accuracy.

This ability is mediated by a large repertoire of olfactory receptors (ORs) expressed on specialized sensory neurons.

ULYSSES replicates this sensing capacity in a synthetic biology framework by introducing selected C. elegans ORs into engineered yeast (Saccharomyces cerevisiae). These ORs are functionally coupled to a bioluminescence resonance energy transfer (BRET)-based biosensing construct. Upon binding cancer-associated VOCs, conformational changes in the ORs trigger measurable BRET signal shifts, serving as indicators of cancer-specific profiles with nanomolar sensitivity. In parallel, urine VOCs will be analysed via gas chromatography–mass spectrometry (GC-MS).

Machine learning will be applied to the spectral data to identify key compounds that differentiate cancer from healthy samples and link them to specific OR activation profiles. Engineered yeast biosensors, each with a distinct OR-BRET construct, will be arrayed on a disposable device. Upon urine exposure, BRET signal changes will be recorded and interpreted via an AI algorithm trained on activation heatmaps. This enables the identification of cancer-related patterns with high sensitivity and specificity. Feasibility is ensured by the convergence of expertise within a strongly interdisciplinary consortium.

ULYSSES lays the foundation for a versatile diagnostic platform with broad applications in health monitoring and personalized medicine, with strong potential for societal and healthcare impact.

Impact

The development of a diagnostic tool that is non-invasive, cost-effective, and user-friendly would represent a transformative advancement in cancer screening. Such a tool could enable early detection of breast and prostate cancers at a scale currently impossible with existing technologies — from mammography and PSA tests to biopsies — which are invasive, expensive, or insufficiently specific.

By harnessing the extraordinary chemosensory sensitivity of C. elegans olfactory receptors — shown to discriminate cancerous from healthy urine with over 90% accuracy — and translating it into an engineered yeast biosensing platform, ULYSSES aims to make early cancer detection as simple and accessible as a home pregnancy test. This has the potential to dramatically improve participation in screening programs, particularly among currently underserved populations, and to reduce the global healthcare burden of late-stage cancer diagnosis.

Beyond breast and prostate cancer, the ULYSSES platform is inherently modular and extensible, opening a pathway toward diagnostics for other hard-to-detect cancers such as pancreatic and lung cancer, as well as broader applications in environmental monitoring, food quality control, and the digitalization of olfaction.

This project is carried out through a collaboration between D-Tails Srl SB (Rome, Italy), the University of Copenhagen (Denmark), University College London (United Kingdom), and the Istituti Fisioterapici Ospitalieri — Regina Elena National Cancer Institute IRCCS (Rome, Italy), with funding from the European Innovation Council (EIC) Pathfinder 2025 programme.

Link at cordis site: https://cordis.europa.eu/project/id/101256857

Partners

EIC funding

Acknowledgement of EIC (EU) funding:

“This project has received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement No 101256857. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Innovation Council and SMEs Executive Agency (EISMEA). Neither the European Union nor the granting authority can be held responsible for them”