  While nucleic-acids can be readily amplified for single-marker detection, a
comparable method for proteins assay is currently unavailable. Proteins
potentiometric detections at 10-20 molar have been demonstrated, but the
mechanism remains elusive. Here, we unveil how pH-conditioning within the
trillions of recognition elements densely packed on a millimeter-large surface,
enables single protein or DNA selective detections in 0.1 mL of a biofluid.
Plasmonic, electronic and surface probing techniques demonstrate that a
conformational change, elicited by a single-affinity binding, alters the
secondary and tertiary structure of the recognition elements. A
phenomenological mechanism foresees that the pH-conditioning initiates a
hydrophobization process leading to the formation of a partially aggregated and
metastable state that facilitates the amplification spreading. Impact on
protein aggregates control and biomarker-based diagnostics, is envisaged.
