Medical diagnosis is currently undergoing a major revolution due to the fast discovery of molecular biomarkers, and the development of multimodal “metabiomarker” signatures. Progress, however, is hindered by low abundance of many biomarkers of interest in body fluids, in absolute concentration and with regard to other biomolecules. The aim of the present project is to apply these progresses in biotechnology, nanoparticle synthesis, and nano-instrumentation to the development of fully integrated lab-on chip instruments able to perform elaborate multimodal biomarker analysis on a routine basis and at the ultrasensitive level required to allow minimally invasive tests. In particular, we aim at overcoming a major bottleneck on the path to this objective, which was identified in a previous project in the “HEALTH” priority: no satisfactory solution currently exists to bridge the several orders of magnitude between the nanoscale volumes at which ultrasensitive new generation sensors operate, and the often millilitre volumes of samples in which the molecules of interest must be found. For this, we shall combine innovations in pre-concentration, micro and nanofluidics, self-assembly, micro-nanofabrication, and nanodetection. The project will develop a generic, multipurpose, platform of compatible enabling technologies, and integrate them into devices. In order to maximize impact and societal benefit, the project will be validated on an application of major interest for health, namely the early detection of biomarkers for neurodegenerative diseases (including Alzheimer), with special emphasis on subtyping of these diseases for improved treatment strategies. The consortium includes a multidisciplinary group of technology developers, three leading biomedical groups in clinical neuroscience for definition of specifications and end-user pre-clinical validation, and three research-oriented SMEs in biotechnology, nanosensing and microfluidics.