TM-REST · A new platform for fast molecular detection of MDR and XDR resistant strains of M. tuberculosis and of drug resistant malaria

Recent developments in molecular tools combined with updated epidemiological data provide novel challenges to the development of modern molecular diagnostics. The increasing threat of infections due to Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections poses important questions that call for development of integrated tools for rapid diagnosis. In the specific case of tuberculosis (TB), an integrated rapid diagnostic approach should be able to allow at the same time species identification, drug susceptibility testing and molecular typing. We propose to develop and validate a silicon-based platform for molecular biology testing consisting in a single disposable device (biochip) and on associated specific instruments (reader). This technology is able to simultaneously serve as a platform for high specificity amplification and hybridisation of selected targets, and to provide the diagnostic report within few hours. Main advancement over existing technology (i.e. Real-Time PCR) consists in the possibility to perform the test at competitive costs, using an higher number of genetic probes by integrating multiple, separate PCR chambers and medium density array (50-200 probes), with faster and more stable amplification and hybridisation reactions through optimised and controlled thermal ramps and profile. In addition to the technology development, special focus will be put on the feasibility and cost-effectiveness of such a novel tool with high technological content for application in countries with high TB, MDR- and XDR-TB incidence. In parallel to the development and validation of the chip-based diagnostic platform for TB, a feasibility study on its applicability to other poverty related diseases such as malaria, will be carried out. In summary, the present proposal aims at developing an affordable, high-tech platform for rapid molecular diagnosis applicable to TB and other infectious and poverty-related diseases