Quantification of antigen by digital domain analysis of integrated nanogap biosensors

Nanogap biosensor shows a distinct conduction change upon sandwich-type immobilization of gold nanoparticle probes onto the gap region in the presence of target biomolecules. Although this large conductance change could be advantageous in distinguishing signal on or off devices, since the extent of conductance change is quite irregular even at the same analyte concentrations, it fails to extract quantitative information from its level of conductance change. In other words, the conductance change of a single device does not reflect the concentration of the target molecule. In this study, we introduce an alternative approach of interpreting the concentration of target molecules using digital domain analysis of integrated nanogap devices, where the fraction of signal-on-devices, or on-device-percentage (ODP), was translated into the concentration of the target molecule. The ODP was found to be closely related to the number density of the immobilized probes and, therefore, to be an excellent measure of the analyte concentration, which was demonstrated in the immuno-selective detection and quantification of influenza A hemagglutinin and prostate specific antigen.