Project: Development of a biological method enabling the very early detection of altered DNA molecules linked to colorectal cancer.

The objective of the project is to develop a non-invasive Colorectal cancer (CRC) very early screening assay, the individual micro-fluidic chips containing the DNA from the patients and the associated instrument to perform the tests based on some of the latest advances in molecular biology, physics, optics, microsystems and information technologies. The consortium is composed of a French Eurostars SME (Droplet Diagnostics) and an Austrian large group (SONY DADC). Droplet Diagnostics is backed-up by the University of Strasbourg where Pr. Griffiths, one of the world leaders in the field of micro-fluidic technology, is leading innovative research._x000D__x000D_Our approach is to move from the cure of the disease to the very early detection in order to prevent the development of this deadly disease. As a consequence of this project, the Healthcare costs to cure patients that represent 30k€-45k€ per patient per year will be significantly reduced._x000D__x000D_SONY DADC, well known for the manufacturing of optical storage media, as well as smart consumables for life science and diagnostics, has entered this project to manage the R&D activities of the micro-fluidic chips._x000D__x000D_Each P will bring to the consortium its expertise and resources in Research, Development and Business Development. Regarding Intellectual Property it has been agreed that Droplet Diagnostics will retain IP on biological and technological deliverables except chip manufacturing that will reCO with SONY DADC._x000D__x000D_CRC is a serious public health problem affecting both men and women (413,000 people were diagnosed in Europe in 2006 resulting in 207,000 deaths; in the USA, 150,000 people were diagnosed in 2008 resulting in 50,000 deaths), yet morbidity and even the need for adjuvant therapy can be prevented if the tumors, or their related DNA biomarkers, are detected at an early stage and if the tumor is removed from the patient before it can metastasize (more than 90% of recovery is reported in that case)._x000D__x000D_The mutation of the APC gene is the first modification that can be detected in the progression of CRC. Mutant APC DNA from tumors has major advantages over other colorectal tumor biomarkers, such as RNA and protein biomarkers, in terms of bio-stability, the ability to amplify the biomarker by PCR, the lack of the biomarker in healthy controls, and the fact that the change in DNA is qualitative rather than quantitative. Importantly, tumor-causing mutations in this gene can be detected in the DNA from the stool of patients that have polyps and early stage tumors (N Engl J Med, Vol. 346, No. 5 January 31, 2002) using mutation specific assays for the APC gene. _x000D__x000D_Clearly what is needed for population-based screening purposes is a high sensitivity routine diagnostic test that can detect most of the mutations in the APC gene leading to colorectal cancer in stool DNA from patients with polyps or pre-metastasized colorectal tumors. _x000D__x000D_We propose to use the Protein Truncation Test (PTT) as a fast and easy means to scan a test sequence for mutations. Unfortunately the standard PTT is a low sensitivity assay that is only capable of detecting mutations representing 30% or more of the DNA sample. The sensitivity problem of the PTT can be overcome by digitizing the assay, that is to say by analyzing a single APC gene at a time in many separate and independent reactions. With such an approach, a mutant gene is easy to detect because it makes up 100% of the analyte in an individual reaction and the sensitivity is limited only by the number of reactions performed, which can be in the millions using recent advances in emulsion chemistry and micro-fluidics. _x000D__x000D_Micro-droplets with a diameter of 1 µm have to be generated to hold one single copy of APC gene fused to its reporter gene. Therefore, micro-fluidic chips capable of the production of 1-5 µm diameter droplets will be developed in this program. The detection of the presence of the reporter gene in the droplet will be performed via fluorescence._x000D__x000D_Within this Eurostars project, an alpha-prototype of the analytical system that comprises the generation of the droplets and their detection will be developed. The design, build and evaluation of this prototype will be the basis of the specification of the future commercial equipment. _x000D__x000D_A large scale clinical evaluation the biological method, micro-fluidic chip and analytical instrument is targeted to follow the completion of this Eurostars project._x000D_The clinical studies have been planned as part of a research program organized with The French Agence Nationale de la Recherche (ANR) as part of a program called "Nanobiotechnology"._x000D__x000D_Depending on the geographical area, commercialization will be organized after the Eurostars project either via licensing to a major player in the diagnostics field or via distribution with a Healthcare professional.

Acronym DropDiag (Reference Number: 6339)
Duration 01/09/2011 - 31/12/2014
Project Topic The DropDiag consortium proposes to develop a highly sensitive innovative test capable of detecting polyp derived DNA, providing a major improvement in non-invasive testing of early stage colorectal tumors. The testing equipment will be developped using micro-fluidic edge technology.
Project Results
(after finalisation)
For Sony the objective of this project was to develop a microfluidic biochip for the detection of early-stage bowel cancer. The critical issue was to develop a fabrication process to include the micro- and macro-structures (wells and fluidic) on a monolithic plastic biochip to keep the price per chip as low as possible. This is crucial for a realistic market impact in the in-vitro diagnostics. We managed to develop such a process with 100 % degree of completition and could set the price per chip to a commercial relevant level._x000D__x000D_
Network Eurostars
Call Eurostars Cut-Off 6

Project partner

Number Name Role Country
2 Droplet Diagnostics SAS Coordinator France
2 Sony DADC Austria AG Partner Austria