Community Research and Development Information Service - CORDIS


ULTRAPLACAD Report Summary

Project ID: 633937
Funded under: H2020-EU.3.1.

Periodic Reporting for period 1 - ULTRAPLACAD (ULTRAsensitive PLAsmonic devices for early CAncer Diagnosis)

Reporting period: 2015-05-01 to 2016-10-31

Summary of the context and overall objectives of the project

Colorectal cancer is a lethal disease responsible for more than 200,000 deaths per year in Europe, with similar absolute numbers for men and women. It is the second most common cancer in Europe in terms of incidence rates (after breast cancer) and also the second cancer in terms of mortality, with only lung cancer contributing more cancer deaths.
Early detection through population screening has been shown to reduce the mortality from colorectal cancer. Unfortunately, colorectal cancer screening campaigns suffer from low compliant rates linked to the invasive currently available diagnostic methods. Standard clinical protocols for people at high risk of developing colorectal cancer detection are based on colonoscopy and tissue biopsy, which involve sampling cells with the use of small-gauge needle. Tissue biopsy is also applied for the surveillance and follow-up of patients with colorectal cancer, and in these cases the procedure is even more invasive, and sometimes technically challenging or even impossible.
Cancer biomarkers circulating in body fluids are widely used, but they lack sensitivity and specificity, reducing their applicative value. This problem has been tackled by attempting to develop cost-effective, highly reliable and minimally-invasive biomarkers and integrated diagnostic approaches. However, barriers remain that prevent a widespread use of these approaches.
ULTRAPLACAD aims at the development of a novel robust in vitro diagnostic system for early cancer diagnosis, prognosis, patient follow-up and therapy efficacy assessment based on molecular analysis of peripheral blood (liquid biopsy).
ULTRAPLACAD is focused at developing a plasmonic-based device with integrated nanostructures for the detection of mutated DNAs, microRNAs and tumor autoantibodies (a-TAAs). The detection of all these molecular cancer biomarkers freely circulating in blood of colorectal cancer patients will be combined in a single device that is expected to overcome hurdles and limitations of the available approaches. ULTRAPLACAD will detect genomic DNA and microRNA with no need for preliminary amplification of the nucleic acid sequences. In addition, a-TAAs will be detected with an improved sensitivity with respect to conventional fluorescence detection platforms.
ULTRAPLACAD will develop a bimodal industrial prototype integrating novel surface plasmon resonance imaging (NESPRI) and plasmon-enhanced fluorescence (PEFSI) sensing technologies, thus providing an unique and up to now unprecedented platform for the comprehensive detection of nucleic acids and protein biomarkers in blood plasma. Automated fabrication processes suitable for low cost mass production will be also developed and applied to produce disposable integrated chips.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Activities of the project are organized in eight work packages (WP), two of which specifically focus on public awareness and exploitation (WP7) and management and coordination (WP8), respectively.
The project activity has started with the identification of technical specifications of ULTRAPLACAD final industrial prototype (WP1).
WP2 activity has been aimed at designing and fabricating the most effective nanostructures in generating optical effects that the ULTRAPLACAD device will exploit. Efficient synthetic probes for the detection of nucleic acid sequences have been also designed and synthesized and procedures for the needed chemical modification of nanostructures have been selected and tested. Nanoparticle enhanced assays that operate with attomolar sensitivity in detecting DNA and femtomolar sensitivity in detecting microRNAs have been also developed.
PEFSI detection of a-TAAs is performed by attaching on PEFSI nanostructures specific thermoresponsive polymers that have been designed and synthesized.
The main objective of WP3 is the development of an industrial prototype of a bimodal reader for NESPRI and PEFSI detection. The first phase of the bimodal reader design and fabrication has been completed.
In WP4 animal models of liquid biopsy have been developed and retrospective cohorts of colorectal carcinoma patient plasma samples have been recruited. A novel, prospective cohort of patients has been also enrolled, organizing an internal minibank comprising tumor tissue, plasma, and purified analytes to be shared among partners.
The development of disposable nanostructured chips for NESPRI and PEFSI (WP5) has started with the development of the integrated microfluidic devices.
The process for the high-volume fabrication of nanostructured disposable chips has been developed and demonstrated. Also the microfluidics part of the disposable chip has been produced by demonstrating the high-volume manufacturing capability. The integration of the nanostructured optical surface and microfluidics part in large-volume production has been also demonstrated.
To summarize main results achieved so far are:
- NESPRI and PEFSI nanostructure geometries have been identified;
- Probes for the selected all-RAS mutations and microRNAs have been synthesized;
- Candidate antigenic peptides for a-TAA detection have been defined;
- Attomolar detection of all-RAS mutations and femtomolar detection of microRNAs have been demonstrated;
- The first version of NESPRI and PEFSI reader laboratory prototypes have been completed;
- The high-volume fabrication of nanostructured disposable chips has been demonstrated.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

ULTRAPLACAD will develop and validate a new plasmonic system for minimal-invasive colorectal cancer diagnosis based on the ultrasensitive analysis of nucleic acids and protein biomarkers circulating in human blood. ULTRAPLACAD will detect genomic DNAs and microRNAs without PCR amplification and a-TAAs with an improved sensitivity with respect to conventional fluorescence detection platforms. These characteristics put ULTRAPLACAD at the forefront of molecular diagnosis technologies as an unique and up to now not existing platform for the comprehensive detection of nucleic acids and protein biomarkers in blood plasma. Moreover, if offers the advantage of reduced sample contaminations, analysis time, assay costs due to reduced complexity of assays and respective readers.
Today’s screening methods for the early detection of cancer in average-risk asymptomatic people are based on invasive methods for colorectal cancer (e.g. colonoscopy). However, these screening methods still represents higher costs between €2,000-3,000/test and, most importantly, due to its logistic and biological complexity, reaches only fraction of population.
Very few FDA approved non-invasive methods for colorectal cancer screening have been available only recently. Therefore the development of tools and procedures for low-cost, minimal invasive and high throughput early detection and management of CRC is therefore still greatly needed.
ULTRAPLACAD diagnostic platform will improve early diagnostic testing and also enable more specific selection of patients for therapy, as well as enables therapy monitoring from liquid biopsies, thus reducing invasive procedures and improving patient management. The development of ULTRAPLACAD platform enables a broad range of clinical applications and is therefore a step to saving thousands of lives and, at the same time, avoiding additional strain on the healthcare systems in developed countries (average cost of detection and annual cost for therapy, which represents approx. 7,2 billion € in Europe only).

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