Label-Free and Selective Single-Molecule Bioelectronic Sensing with a Millimeter-Wide Self-Assembled Monolayer of Anti-Immunoglobulins

Immunoglobulin M (IgM) single-molecule and label-free detection is demonstrated, for the first time, by means of an electrolyte-gated thin-film transistor. The sensor integrates a millimeter-wide self-assembled monolayer (SAM) that includes trillions of anti-IgM capturing proteins. This adds generality to the already introduced single molecule with a transistor (SiMoT) platform. Besides the extremely high sensitivity, the SAM confers to the SiMoT bioelectronic sensor a high selectivity that is here assessed by measuring the differential responses of the IgM or the immunoglobulin G (IgG) cognate biomarkers mutually interacting with anti-IgM or anti-IgG capturing SAMs. At the same time, no response to IgG or IgM is measured with the anti-IgM or anti-IgG SAM, respectively. The SiMoT technology is known to exploit the hydrogen bonding network present in the SAM. In this paper, further elements supporting the model of this network enabling single-molecule sensitivity are provided by demonstrating that, once this electrostatic connecting element is removed, the sensing is suppressed. It also provides a plausible explanation of the wide-field single-molecule sensing mechanism in terms of the amplified field-effect response and propagation of electrostatic domains associated with the electrostatic hydrogen bonding network. Future possible applications to low-cost early detection of infection diseases can be envisaged.