Peptimprint relies on the complementarity and expertise of five teams specialized in the conception of bioactive compounds (Partner 1-IBMM-team amino acids), analytical development (Partner 1-IBMM-team analytical sciences), sol-gel process and hybrid materials (Partner 2-ICG-team CMOS), microfluidics devices (Partner 3-L2C-team POMM) and study of biomolecular interactions by biosensors development (Partner 4-IRCM-team criblage) Objectives The main objective of Peptimprint is to set-up a ground-breaking technology to prepare specific tridimensional and functionalized imprints of peptides and large proteins by sol-gel process, polymerizing original hybrid building blocks mimicking amino acids around the biomolecular template. Unfunctionalized blocks (e.g. tetraethoxysilane, dimethyldichlorosilane) will be used concomitantly to create the network. Once the template biomolecule removed, the hollow cavities will be able to capture these biomolecules with very high selectivity. The second objective of Peptimprint is the preparation of unprecedented imprinted devices for the detection, separation of biomolecules and their extraction and concentration in biological samples. Surface Plasmon Resonance (SPR) and Quartz Crystal Microbalance (QCM) chips as well as polydimethylsiloxane (PDMS) based microfluidics channels will be modified with hybrid biomimetic imprints. Scientific challenges Classical molecular imprinted polymers (MIPs) suffer important limitations. Firstly, the polymerization conditions (organic solvents, non-selectivity vs amino acid side-chains…) affect the structure of the template yielding a non-relevant MIPs. Secondly, the obtainment of a large cavities deprived of functional groups generate non-specific imprints that failed to mimic the diversity of weak interactions found in natural recognitions systems. Peptimprint approach is bringing down such barriers. The sol-gel process takes place at physiological pH, in aqueous conditions and at room temperature preserving the structural and functional integrity of the protein template. Moreover, the original hybrid monomers (amino acid mimics) used in Peptimprint will recapitulate all types of interactions (ionic/hydrogen bonding/hydrophobic/aromatic stacking) involved in real interactions between biomolecules. Proceeding much more slowly than photopolymerization used in classical MIPS, sol-gel approach of Peptimprint favours a self-organization of all the functionalized hybrid blocks around the template. First models and applications Several peptide and proteins templates covering a wide range of size (from 1.5 to 150 kDa) and functions will be used as models for Peptimprint. It includes vancomycin, C-peptide, human kallikrein1, antibody fragments and therapeutic antibody. Hybrid imprints of such proteins will be prepared on the surface of QCM and SPR devices and the interaction will be studied. On the other hand, models will be either adsorbed or covalently grafted on the silicon mold to cast hybrid-PDMS microchannels. The later will be used for electrophoric analyses. Expected impacts Fundamental knowledge on molecular imprinting will be gathered thanks to Peptimprint project including (i) a generic and straightforward sol-gel method and (ii) tailored reagents (hybrid amino acids) for the inorganic polymerization of functionalized imprints. From a technological point of view, if convincing analytical data are obtained using imprinted microfluidics devices or sensors, the development of relevant selective sensors for the detection and the quantification of biomarkers will be envisioned. Indeed, Peptimprint concept can be generalized to any other types of biomolecules (oligosaccharides, oligonucleotides etc.) or even objects (viruses, bacteria) enlarging the scope of biomedical applications. A strategic advisory board will be gathered (month 24) to discuss the technological transfer opportunities and to maximize the dissemination impact.