Sizing Single Particles at the Orifice of a Nanopipette

Developing new methods and techniques for the size analysis of particles in a solution is highly desirable not only for the industrial screening of particles but also for single biological entity analysis (e.g., single cells or single vesicles). Herein, we report a new technique for sizing single particles in a solution with a nanopipette. The rationale is essentially based on ion-current blockage when the particles approach the proximity of a nanopipette orifice. By rationally controlling the geometry of the nanopipette and the applied potential, the spike-type ion current transient generated from the motion of particles in the process of "collision and departure" is employed for sizing single particles. The results show that both the relative ion-current change (ΔI/I₀) and the dwell time (Δt) of spike-type transient are dependent on particle size. Differently, Δt is also related to an externally applied voltage. Statistical analysis shows that ΔI/I₀ is proportional to the particle diameter, and this linear relationship is further understood by finite-element simulations. This study not only provides a new principle for sizing single particles in a solution but also is helpful to understand the motion of a particle near the orifice of the nanopipette.