Ongoing changes in medical care for complex diseases and patients conditions are demanding novel technological diagnostic tools that could enable quick, accurate, reliable and cost-effective results so that appropriate treatments can be implemented in time, leading to improved clinical outcome. For this reason, this proposal aims at the development of an advanced diagnostic tool for biological analysis able to handle and directly analyse minimum amounts of biological fluids without previous labeling procedures, detecting target molecules in their natural form, without alterations. A technological breakdown is expected by the integration on a single photonic platfom of multiple functionalities rendering in a biosensor lab-on-a-chip of improved performance in terms of sensitivity and multiplexed analysis.
The novel diagnostic platform will include micro/nanophotonic biosensors integrated with microfluidics, light incoupling in sub-micron channels, custom-designed photodetectors, data acquisition and processing electronics. The diagnostic tool will be designed to overcome the limitations of current conventional techniques by offering the required sensitivity, parallel detection, easy handling, portability and low sample volume. The photonic sensors will be based on novel nanophotonic bimodal waveguides based on silicon technology and will have, as main characteristic, an extreme sensitivity which will allow the detection of very low concentrations (pico/femtomolar and possibility of single-molecule) of the analyte to be tested.
As a proof of concept for demonstrating the outstanding performance of the tool, the platform will be applied to monitor FAS gene expression at several cellular pathways levels such as: (i) splicing routes and splicing variants levels, (ii) DNA methylation, (iii) interaction with non-coding RNA regulators such as microRNAs. This approach could be of relevance for diagnostics and prediction of response to cancer treatment of acute myeloid leukemia (AML) patients. It would allow the further identification of defective pathways which could enable the design of therapies to overcome the apoptosis-resistance of tumors thereby improving the clinical outcome in AML patients when used in combination with standard chemotherapy.