Future breakthroughs in the understanding of fundamental biological processes causing major diseases are expected from the development of miniaturized probes or microscopes able to detect and identify a single or a small number of molecules. The SingleMoleculeDetection (SMD) proposal will develop a unique device able to perform simultaneously and in a dynamic way force and spectroscopic measurements. We will design and fabricate novel devices for the generation of plasmon polaritons as well as combine photonic crystals and plasmonic nanolenses. These new devices will be able to detect few/single molecules through Raman, InfraRed and Terahertz (THz) signals and in combination with Atomic Force Microscopy and Optical Tweezer force spectroscopy with a spatial resolution in the sub-10 nm for Raman and IR and sub-100 nm for the THz region. The complete characterization of single unknown molecule will be demonstrated through: i- investigations on the chemical and physical properties of membrane receptors, such as rhodopsin, odorant receptors and ionic channels; ii- identification of new molecules involved in cancer development and metastasis. The new devices will allow the acquisition of THz images and we will explore the possibilities of this new spectral region for biomedical scanning. The SMD proposal is based on an original idea of the coordinator, prof. E. di Fabrizio and will be exploited thanks to the complementary expertise present in the different sites and to a tight coordination between the various groups. The design, fabrication and testing will be performed at UMG, TASC and CBM Integration in a single instrument will be carried out at TASC, CBM, IIT Nanotec, RUB. Validation activities will be performed by all the partners taking advantage of the world leading expertise of the TUDO and the STRATH- AC in spectroscopy of natural and artificial biological systems. The SME NANOTEC and CBM will provide the commercial exploitation of the obtained results.