Biomarkers are measurable indicators of a particular disease state of an organism. There has been an increasing demand for diagnostic markers, enabling reliable and non-invasive screening of peripheral biofluids. It is also established that a universal screening against life-threatening diseases, such as cancer, or infectious disease outbreaks, can be accomplished only by combining genomic and protein marker-based tests. The NoOne project aims at conceiving, engineering, fabricating and validating a ground-breaking platform based on a single-molecule binary bioelectronic sensor, capable to reliably discriminate biofluid samples enclosing zero biomarkers from those containing just one. The technology can be used for ultimate binary sensing of both proteins/peptides and genomic markers to enable the reliable screening of diseases such as cancer as well as viral and bacterial infections. The NoOne binary platform is designed to be portable, cost-effective, easy to operate and with a time-to-results within one hour; hence it is the ideal candidate for point-of-care applications. The prototype will enable clinicians, phytopathologists or veterinaries, to identify the set of samples that are totally free from a protein, peptide or genomic marker as well as from a pathogen (virus or bacteria), from those enclosing at least one with a confidence level of 99%. This makes the NoOne platform the best performing ever in enabling a fast, highly reliable, cost-effective identification of the subset of biological samples belonging to the potentially diseased part of a population. This is of paramount importance for predictive screening of humans, plants or animals. NoOne will demonstrate its effectiveness in key relevant applications such as the binary detection of pancreatic cancer biomarkers, SARS-CoV-2 virus, the Xylella Fastidiosa bacterium and the assay of post translational peptides evidencing the phosphorylated forms regulating crosstalk with oncogenic signalling pathways.