MIRACLE

An FP7 EU Funded R&D Project

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The FP7 funded project "Body-on-a-Chip" aims at developing a versatile and reconfigurable pharmaceutical screening technology platform that relies on organotypic three-dimensional spherical micro-tissues. This platform will accommodate different types of human micro-tissues (tumour, brain, liver, heart etc.) and feature microfluidic interconnection between these tissues, thus mimicking the physiological context and conditions in a human body. Dosage of components or candidate drugs to, e.g., liver tissue will lead to the generation of metabolic products in the respective tissue compartment.
These products then can be routed via the microfluidics to, e.g., connective tissue to assess the efficacy of the candidate drug and related adverse toxicological effects on the target tissue and functionally related tissues. This way, functional connectivity in a real body can be mimicked at the desired level of complexity, and the effects of drugs can be comprehensively assessed.

The COCHISE project, which ended in 2009, was directed towards the development of Cell-on-chip biosensor for detection of cell-to-cell interactions. It was the first step of an activity aimed at the development of enabling micro-technologies to monitor physiological cellular interactions at the single cell level with a high throughput. It's use is for immunological monitoring of anti-tumour vaccinations, singling out the rare effector cells (in the order of 10-3) that are actually active against tumour cells. The sensor consists of an orderly matrix of about 4,000 living cells deposited in microwells created in a biocompatible substrate that also serves as a high-density circuit board. An important side of the research is the definition of new therapeutic and diagnostic protocols for the immunotherapy of cancer.

In the FP7 project HAMAM researchers will work on both early detection and accurate diagnosis of breast cancer which are still unresolved challenges. Today, a variety of imaging modalities and image-guided biopsy procedures exist to identify and characterize morphology and function of suspicious breast tissue. However, a clinically feasible solution for breast imaging, which is both highly sensitive and specific with respect to breast cancer, is still missing. As a consequence, unnecessary biopsies are taken and tumours frequently go undetected until a stage where therapy is costly or unsuccessful. HAMAM will tackle this challenge by providing a means to seamlessly integrate the available multi-modal images and the patient information on a single clinical workstation. Based on knowledge gained from a large multi-disciplinary database, populated within the scope of this project, suspicious breast tissue will be characterised and classified.

The FP7 ICT project NeoMark is about to enable prediction of cancer reoccurrence by recording and combining heterogeneous clinical, laboratory, molecular and imaging data to develop a data integration environment facilitating multiscale and multilevel modelling. NeoMark will pursue the identification of imaging and genomic/ proteomic markers aimed at modelling recurrence of neoplastic disease with two major clinical/scientific purposes: (1) identify subjects at higher risk of reoccurrence after reaching remission; (2) early diagnose the presence of a reoccurrence.
The technical target of NeoMark will be the development of two functional environments: one for the definition of biomarker profiles and one for the follow-up of the evolution of the disease.
NeoMark expects to develop a system able to early detect the “markers” specific for oral cancer and so enable:
• early and more specific diagnosis of cancer reoccurrences;
• more targeted and effective interventions based on the patient-specific disease profile;
• avoiding unnecessary treatments for patients at very low risk of reoccurrence;
• optimising the work of physicians and the usage of resources;
• improving the scientific and medical knowledge on oral cancer processes;
• improve patients’ quality of life;
• increase the life duration for patients with cancer reoccurrence.

The EU- co-financed project "Integrated MicroNano-Opto Fluidic systems for high-content-diagnosis and studies of rare cancer cells" (CAMINEMS) has developed an innovative tool which is able to perform a detailed molecular characterization of CTCs as a kind of "liquid biopsy". 9 partners from 5 countries participated and were funded with 3.5 mio € to research on a high-resolution medical imaging system for in situ fluorescence hybridisations (FISH) for captured CTCs.

ML2 - MultiLayer MicroLab will provide a design and manufacturing platform for the production of sophisticated devices which combine microfluidics, optics and microelectronics. ML2 devices will be compact devices with increased performance at lower prices while providing higher sensitivity compared to existing Micro-Nano Bio Systems. The packaging method and fully automated production will lead to higher reproducibility, increased integration of bioactive components and higher intelligence of the devices.

Through further development, integration and validation of micro-nano-bio and biophotonics systems from previous projects CanDo will develop an instrument that will permit the identification and concentration determination of rare cells in peripheral blood for two key societal challenges, early and low cost anti-cancer drug efficacy determination and cancer diagnosis/monitoring.A cellular link between the primary malignant tumor and the peripheral metastases, responsible for 90% of cancer-related deaths, has been established in the form of circulating tumor cells (CTCs) in peripheral blood. Furthermore the relatively short survival time of CTCs in peripheral blood means that their detection is indicative of tumor progression thereby providing in addition to a prognostic value an evaluation of therapeutic efficacy and early recognition of tumor progression in theranostics. In cancer patients however blood concentrations are very low (=1 CTC/1E9 cells) and current detection strategies are too insensitive, limiting use to prognosis of only those with advanced metastatic cancer. Similarly problems occur in therapeutics with anti-cancer drug development leading to lengthy and costly trials often preventing access to market. There is therefore a clear need for a novel analytical platform capable of highly reproducible and reliable identification of CTC concentrations of interest in an easily accessible format.With all relevant industrial stakeholders and users onboard CanDo is uniquely capable of delivering such a platform. Its novel cell separation/SERS analysis technologies plus nucleic acid based molecular characterization will provide an accurate CTC count with high throughput and high yield meeting both key societal challenges. Being beyond the state of art it will lead to substantial share gains not just in the high end markets of drug discovery and cancer diagnostics but due to modular technologies in others e.g. transport, security and safety and environment.

The MIRACLE project is to be seen in context and in synergy with other EC funded projects: