Single-molecule detection with a millimetre-sized transistor.

Macchia, Eleonora; Manoli, Kyriaki; Holzer, Brigitte; Di Franco, Cinzia; Ghittorelli, Matteo; Torricelli, Fabrizio; Alberga, Domenico; Mangiatordi, Giuseppe Felice et al. · Nat Commun · 2018

basic_science · Level V

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Abstract

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 10<sup>12</sup> 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.

Medical subject headings