Competitive Impedance Spectroscopy in a Schottky-Contacted ZnO Nanorod Structure for Ultrasensitive and Specific Biosensing in a Physiological Analyte

To enable detection and discovery of biomarkers, development of label-free, ultrasensitive, and specific sensors is the need of the hour. For addressing this requirement, here, a Schottky-contacted ZnO nanorod biosensor has been demonstrated, which explores the interplay between Schottky junction capacitance and solution resistance, resulting in an interesting sensing principle of competitive impedance spectroscopy. When the transition of dominating impedance occurs from solution resistance to junction capacitance, a notch or a peak appears in the impedance response at a particular frequency (referred to as the corner frequency) depending on the charge of the target molecule. The appearance of the peak or notch acts like an electronic label for selectivity since it is visible only for target molecules even at ultralow concentrations in the physiological analyte, where the magnitude of impedance change overlaps with that for nonspecific molecules. This phenomenon has been successfully applied for the positively charged vascular endothelial growth factor (VEGF) and the negatively charged hepatitis B surface antigen (HBsAg), where the shifts in the higher corner frequencies for 1 aM concentration of the target molecules have been observed to be more than 3 times the changes in the impedance magnitude. Further, the area of the ZnO nanorods was segmented into two zones corresponding to the lower and higher concentration regimes, thereby expanding the dynamic range. To summarize, an ultralow detection limit of 1 aM with a dynamic range up to 1 pM was achieved for VEGF and HBsAg, which is 4 orders of magnitude and 20 times lower than their most sensitive label-free reports, respectively.