Innovative Enabling Micro-Nano-Bio-technologies for Implantable systems in molecular medicine and personalized therapy – Project prolongation

A biochip system capable of continuous monitoring of drugs and biomarkers in blood, or in sub-cutaneous districts, constitutes a major breakthrough in molecular medicine for per-sonalizing therapy of complex diseases. The global aim of the present research is to undertake a multidisciplinary approach to substantially advance the state-of-the-art of on-line-monitoring implantable-devices in personalized medicine. In the previous sinergia project, we have developed components and systems for measuring inflammatory mediators and drugs. These results and progresses have been published in peer-reviewed international journals with high impact factor, as well as communicated at international meetings, and presented in keynote speeches. Nevertheless, the proposed technology has generated new challenges; we believe these novel technological issues merit to be specifically addressed. In particular: (i) some tested drugs revealed to be interfering on the same sensors based on the P450 cytochromes; (ii) the possibility to specifically design the P450 cytochromes opens to improve the drug/probe interactions on the sensor array; (iii) the designed remote powering system is able to supply the required energy but an external control unit is desirable to optimize the energy transfer; (iv) the need of a better following of the disease prognosis requires identifying better molecular mark-ers. Therefore, we propose herein a further research plan to specifically address these newly emerged issues. Moreover, this new research plan will allow the PhD students involved in the previous project to successfully complete their doctoral programs. The aim of this project is to address the novel issues listed above that emerged during the first stage of the research. To this end, the following specific goals will be pursued during the project prolongation:(i) Development of innovative multi-panel sensor array towards simultaneous detection of both disease metabolites and multiple drugs, including linear and other approaches to improve sensors specificity at level of system integration, (ii) Design and implementation of an external control unit to improve the efficiency of the Remote Powering System for the final tests in vivo with Freely Moving Mice (iii) Monitor active drugs and new biomarkers concentration in vivo opening to a dra-matic improve of the compliance of therapeutic regimens for diseases with com-plex pathogenesis,(iv) Design, cloning, and expressing mutants of some probe P450 isoforms in order to improve the enzymes-substrates kinetics to ameliorate the performance of the multi-panel sensor array.The project requires a strong synergy between sensors/CMOS/bio/medical technolo-gies. The project partnership includes experts on:(i) Nano-sensing array at system level with special focus on improved specificity (S.Carrara/EPFL - Engineering/sensors-technology), (ii) Chip fabrication with focus on implantable systems and optimization of the power ef-ficiency transfer (Dehollain/EPFL - Engineering/VLSI design), (iii) Pathophysiology of T-cells for therapy of autoimmune diseases and search for new disease markers (Grassi/IRB - biomedical/T cell physiology and intercellular commu-nications), (iv) Enzyme kinetics and new probes design and expression for improved drugs detec-tion (von Mandach’s goup/Univ. Hospital of Zurich - biomedical/Pharmacology)