SMARTCANCERSENS · Micro/nanosensors for early cancer warning system - diagnostic and prognostic information

Micro/nanosensors for early cancer warning system - diagnostic and prognostic information

The primary objective of this proposal was to establish a multi-annual joint research programme which exploits an international and interdisciplinary consortium of leading research teams from EU Member States and Third countries. This synergistic network of excellence proves to be essential for delivery of multidisciplinary research, innovation and technology transfer in the areas of micro/nano sensors R&D for early cancer warning systems. Such electronic diagnostic tools were based on semiconductor and metallic micro/nano structures for disease biomarkers such as formaldehyde, citrate, biogenic amines (mono, di and polyamines, N-acetyl amines), metal ions (iron, copper, cobalt, cadmium, zinc and nickel), activities/concentrations of amine oxidases, dehydrogenases, phosphatases, arginase and glutathione-S-transferase, protein biomarkers and cancer cells. The project was based on mutually beneficial research strategies and contributed significantly to integration of related research activity from a wide geographic area. The international and interdisciplinary Consortium of research teams, who came together in order to establish the objectives outlined above are composed of six EU Member States (Ireland, Romania, Spain, Portugal, Sweden and France). The exchanges are between these countries and four other organizations located in four different countries with an S&T Agreement, which are Ukraine, South Africa, Egypt, and Tunisia. Three of these countries (Ukraine, Egypt and Tunisia) are also listed among the countries covered by the European Neighbourhood Policy (ENP) and the latter two have become recently associated countries. In order to leverage existing activity within the consortium in the field of biosensors for cancer biomarkers target analytes/biomarkers spanned the following priority groups: 1. Transition metal and inorganic species e.g. Fe, Cu, Cd, Zn, Cr, Pb, Hg, nitrite, citrate, perchlorate, superoxides. 2. Small molecules e.g. L-arginine, urea, creatinine, pyruvate, choline, glutathione, phenol, ammonia/ ammonium ions, formaldehyde and peptides; 3. Protein biomarkers e.g. cytokines, interleukin 8 antigen, breast cancer HER2/neu oncogene TNF, cathepsin D, myeloperoxidase, ferritin, melanoma inhibitory activity protein, α fetoprotein, carcinoembryonic antigen, prostate specific antigen, urokinase plasminogen activator, Human papilloma virus (a precursor to cervical cancer) and enzyme activities e.g. glutathione S transferase, tyrosinase, lactate dehydrogenase, acid phosphatase, arginase and arginine deiminase; 4. Tumour circulating cells and miRNA. Such biomarkers of disease are implicated in cancer of the breast, neck, head, thyroid gland, liver, lung, prostate gland, ovary, cervical, pancreatic carcinoma, glyoblastoma and many tumours of neuroectodermal origin etc. Research activity has focused on evaluation of recognition molecules for the detection process, recombinant yeast enzymes - formaldehyde dehydrogenase and arginase/arginine deaminase, lactate dehydrogenase, ionophores e.g. metal (Co, Fe, Cu) phthalocyanine electrocatalysts and monoclonal antibodies/aptamers/DNA/mRNA. Such biomaterials have been immobilised onto conducting transducer surfaces (Au, Pt, C thin/thick film sensor arrays) via cross-linking, co-deposition with polymers, sol gels, ionic liquids, covalent attachment and formation of self-assembled films. The increase in electronic sensor output caused by enzymatic or chemical transformations is proportional to the target molecule concentration in the sample matrix (blood/urine/tissue). The sensitivity, selectivity, specificity, dynamic range of response, reliability and operational/storage stability of the devices was being thoroughly tested and optimised. Special attention has been paid to the synthesis and immobilisation of recognition molecules in the presence of redox active nano-objects with the view of creating nano-sized recognition membranes with enhanced sensitivity to the target molecules in question. Work has also progressed towards drug therapeutic monitoring (tamoxifen), the fully printed instrument as an integrated biosensor platform, electrochemical lateral flow technology and exploitation of mobile phone interfaces for chemosensing. The in situ detection of cancer cells based on selective binding at an aptasensor followed by label-free detection was also under review. This array of methodologies and technologies represents a unique combination of knowledge across the Consortium partners, which guarantees not only complementary expertise, but also differentiation, and has filled gaps in knowledge spanning fundamental to translational and applied research. Some of the outputs from this transfer of knowledge are given below: • Each researcher within the exchange programme had the opportunity to enjoy specialist/generic training, strengthening core expertise within the partner institutions; • There has been multiple opportunities for testing new materials for biosensor development as components of smart integrated devices with a range of biomedical applications; • Upon successful assembly and integration of the micro/nanosensors, the organisations and their research teams have gained diverse knowledge in different fields of R&D activity, particularly in terms of synthesis, surface modification and characterisation techniques, lithography, and importantly specific requirements for clinical validation and commercialisation of the developed device/s. This has formed the basis for spin-off proposals and will seed new programmes of research across the consortium. • The planned clinical input via ethically approved hospital samples directed the biomedical relevance of the research effort, enabling sample acquisition and validation in the end user environment. • The knowledge transfer will have a lasting influence on scientific activities within the individual partner institutions, resulting in measureable impacts in related research areas and 4th level teaching and learning. Three significant knowledge transfer events were held over the course of the project in Kiev, Ukraine during May 2013, Sousse Tunisia November 2014 and Sweden May 2016. All were well organised, well attended, successful, international scientific workshops and consortium meetings with a wide ranging discussion and dissemination of SMARTCANCERSENS project research activity. The final face to face manager meeting was in May 2016 as a post-symposium event following World Congress on Biosensors, Gothenburg, Sweden, 25-27th May 2016.

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