Pressure-Controlled Nanopipette Sensing in the Asymmetric-Conductivity Configuration

Nanopipettes are important tools across diverse disciplines, including biology, physics, and materials science. Precisely controlling their characteristics is crucial for many applications. Recent progress in this endeavor has involved using the asymmetric-conductivity configuration with different electrolyte solutions inside and outside the nanopipette, which can greatly improve nanopipette sensing. However, understanding such measurements remains challenging due to the complex interplay of diffusion, electromigration, and electroosmosis. Here, we systematically explore a fundamental regime of the asymmetric-conductivity configuration where classical ion current rectification due to ion-selective migration is minimized and 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 optimize the sensitivity in the asymmetric-conductivity configuration, we introduced a method that uses external pressure to control the fluid flow rates at the aperture, tuning the local ionic environment <i>in situ</i>.