Pressure-Controlled Nanopipette Sensing in the Asymmetric-Conductivity Configuration

Nanopipettes are important tools across diverse disciplines including biology, physics, materials science, and electrochemistry, and precisely adjusting their characteristics is vital for many applications. Recent progress in this endeavor has involved using the asymmetric-conductivity configuration with different electrolyte solutions inside and outside of the nanopipette, which can greatly improve nanopipette sensing. However, understanding such measurements is challenging due to the complex interplay between diffusion, electromigration, and electroosmosis. Herein, we studied the simplified case of the asymmetric-conductivity configuration where classical ion current rectification due to ion-selective migration is minimized, while the effect of electroosmotic flow is maximized. We characterized the current-potential and current-distance relationship and revealed that this experimental configuration exhibits many of the characteristics of traditionally rectifying nanopipettes, such as surface charge sensitivity, while the current response can be understood simply from the rate and direction of solution mixing due to electroosmotic flow. To further improve the use of the asymmetric-conductivity configuration, a method was developed using external pressure to control the fluid flow rates at the aperture to tune the local ionic environment in situ, paving the way for novel, more reliable, and higher throughput nanopipette measurements.