Cancer biomarkers circulating in body fluids can be used for diagnosis and treatment monitoring. However, current detection technology lacks the required sensitivity, limiting biomarker use in clinical applications.

Colorectal cancer is the second most common cancer in Europe with respect to incidence and mortality. Although early detection significantly improves outcome, screening compliance in the wider population is low due to the invasive nature of the colonoscopy procedure.

To facilitate prompt cancer diagnosis, the EU-funded ULTRAPLACAD project developed an in vitro platform for the detection of cancer nucleic acid and protein biomarkers circulating in the blood. “The idea was to improve biomarker detection sensitivity by a factor of 1 000, reduce the cost four-fold and the analysis time down to 1 hour,″ explains project coordinator Prof. Giuseppe Spoto of the University of Catania in Italy. The project team involved 13 partners across Europe with cross-disciplinary competencies, including pioneers in surface plasmon resonance.

Innovative technologies

The ULTRAPLACAD device has been designed to integrate a microfluidic circuit with functionalised nanostructure chips. It combines nanostructure-enhanced surface plasmon resonance imaging (NESPRI) and plasmon-enhanced fluorescence spectroscopy imaging (PEFSI). These two novel sensing technologies provide ultrasensitive detection and reduce the need for sample chemical modifications.

Chip design, surface architecture and chemical functionalisation of nanostructures facilitate the simultaneous measurement of multiple markers. For efficient nucleic acid detection, such as Ras mutations and miRNAs, specific probes have been synthesised. The disposable chips are mass produced through an automated fabrication process, which brings down the cost of the assay.

Traditionally, detection of minute amounts of DNA released in body fluids by tumour cells necessitates a pre-amplification step by polymerase chain reaction. The novelty of ULTRAPLACAD lies in the detection assays that do not require enzymatic amplification of DNA in liquid biopsies, thereby avoiding potential errors.

A bimodal reader for NESPRI and PEFSI technologies makes the ULTRAPLACAD device unique and improves the overall detection process even further. As Dr Spoto emphasises “the main advantage of the device is that it can detect both nucleic acids and protein using one single equipment operating with disposable chips.″

The ULTRAPLACAD prototype has been validated using animal models and samples from colorectal cancer patients. Results demonstrate that the sensitivity of the device exceeds conventional detection platforms and the whole assay is faster and simpler in its implementation.

The future of ULTRAPLACAD

Undoubtedly, the combined detection of cancer DNA sequences and selected tumour autoantibodies provide an effective cancer detection approach. ULTRAPLACAD offers a unique platform that can detect both DNA and protein cancer biomarkers, simplifying the process of diagnosis and patient follow-up.

Considering the limitations of existing colorectal cancer screening choices, ULTRAPLACAD offers a non-invasive alternative solution for average-risk asymptomatic people. As such, it will reduce the number of invasive procedures, cut down healthcare costs, and improve patient compliance and management.

Although the platform was specifically fabricated for early diagnosis and prognosis of colorectal cancer, its application can extend to other types of cancer. Long-term, it is also expected to determine the molecular heterogeneity of individual tumours, helping disease stratification and personalised therapy. In view of the future, Prof. Spoto envisages “the ULTRAPLACAD device will contribute to revolutionise molecular diagnosis of cancer and make a difference in cancer care.″