"The main goal of this proposal is to introduce innovative devices and protocols (based on nano- manipulation, the response of micro-(nano-)mechanical oscillators and nano-fluidics) to carry out, precise, high throughput, high sensitivity, and low cost interactomic measurements. We aim at measuring, in parallel, the concentration of up to several proteins or non-coding RNA molecules, in samples down to the single cell level, following the real time concentrations of several biomarkers in patient-derived samples down to femto-molar concentrations, and single-circulating-tumor-cell resolution. We plan to develop our program a) by applying the principles and practice of intrinsically differential measurements, e.g. by building a self-assembled nano-devices that provide robust outputs measurable with topographic AFM imaging, electrochemical measurements, or gel electrophoresis, and b) by using the vertical equivalent of cantilever oscillators (pillars) that we plan to use as quartz “microbalances” that are 10,000 time more sensitive than cantilevers w. r. t. measurable min. mass and 100 time more sensitive w. r. t. dilution. The proposal’s core strategy is to exploit the PI’s expertise in innovative instrumentation and his integrated physical chemistry know-how, leading a highly multi-disciplinary staff to closely interact with first class medical staff in hospital settings to solve, and validate the solution of, relevant medical problems by generating innovative and versatile sensing devices. For instance, the sensitivity of our sensors will allow protein or miRNA analysis from very small and homogeneous samples of tumor cells, as well as the ease identification circulating tumor cells (CTCs) for, in addition to improved cancer diagnostics, also the prediction of patient response to treatment. The convergence between chemistry and biology, through nanotechnology, physics and computational approaches, with medical diagnostics will enable our team to come up with more versatile and reliable diagnostic tools, while stimulating fundamental research in fields as diverse as stem cells differentiation and the study of cell physiopathology."