Luisa Torsi1 Eleonora Macchia1 Kyriaki Manoli1 Brigitte Holtzed1 Cinzia Di Franco2 Matteo Ghittorelli3 Fabrizio Torricelli3 Domenico Alberga2 Giuseppe Mangiatordi2 Gerardo Palazzo1 Gaetano Scamarcio2

1, Chemistry, Università degli Studi di Bari Aldo Moro, Bari, , Italy
2, Università degli Studi di Bari Aldo Moro, Bari, , Italy
3, Università degli Studi di Brescia, Brescia, , Italy

Label-free single-molecule detection has been achieved so far by funnelling a large number of ligands into a sequence of single-binding events with few recognition elements host on nanometric transducers. Such approaches are inherently unable to sense a cue in a bulk milieu. Conceptualizing cells’ ability to sense at the physical limit by means of highly-packed recognition elements, a millimetric sized field-effect-transistor is used to detect a single molecule. To this end, the gate is bio-functionalized with a self-assembled-monolayer of trillions of capturing anti-Immunoglobulin-G and is endowed with a hydrogen-bonding network enabling cooperative-interactions. The selective and label-free single-molecule IgG detection is strikingly demonstrated in diluted saliva while 15 IgGs are assayed in whole serum. The suggested sensing mechanism triggered by the affinity binding event, involves a work-function change that is assumed to propagate in the gating-field through the electrostatic hydrogen-bonding network. The proposed immunoassay platform is general and can revolutionize the current approach to protein detection.