Tuning IonCurrent Rectifying Nanopipettes for SensitiveDetection of Methicillin-Resistant <i>Staphylococcus aureus</i>

Infectious diseases pose a growing challenge in healthcare, with the increasing rate of antimicrobial resistance limiting therapeutic options available for treatment. Rapid detection of infections at the earliest opportunity can significantly improve patient outcomes. In this report, ion current rectifying quartz nanopipettes with ca. 109 nm orifices were utilized for the label-free detection of DNA indicative of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). By immobilizing probe DNA complementary to the <i>mecA</i> gene on the internal walls of the nanopipette, the detection was achieved by monitoring changes in ion current rectification (ICR) following probe–target hybridization. We demonstrate enhanced sensitivity by controlling the surface probe density, resulting in a tunable, sensitive sensor technology with a detection limit as low as 0.35 pM. Finite element simulations are used to support our experimental findings, revealing that to maximize target-induced changes to ICR, the probe surface density must be minimized. This sensitive and label-free methodology was integrated with the polymerase chain amplification reaction to achieve selective identification of this pathogen from laboratory-grown cultures, highlighting that ion current rectifying nanopipette sensors offer the potential to be a cost-effective and rapid tools for infectious disease detection.