Blood contains a treasure trove of proteins biomarkers, most of them still to discover and that it will be crucial for early detection of cancer. A key point to achieve this goal is a technology capable of ‘finding’ ultralow concentrations of protein biomarkers secreted by the tumor to the blood stream in a ‘haystack’ of plasma proteins. Here we show an emergent technology that combines new physical phenomena at the frontier between nanoptics and nanomechanics for detecting low abundance protein-biomarkers. A detection limit of 1 × 10−16 g ml−1 in serum was achieved with prostate specific antigen (PSA), which is at least seven orders of magnitude lower than that achieved in routine clinical practice.