Characterizing Solid-State Nanopore Surface Potential and the Impact of Selective Polymer Coatings to Unravel Clogging

Solid-state nanopores have emerged as powerful tools for single-molecule analysis, with applications ranging from genomics to diagnostics. However, challenges such as surface interactions and clogging have limited their applicability, and a better characterization of the nanopore wall surfaces would provide valuable information to tackle these problems. Here, we present a platform capable of performing high-pressure streaming current measurements in the picoampere range, to characterize the surface potential of solid-state nanopores. By examining different operating conditions, such as pore diameter, salt concentration, and pH, we discuss optimizations for precise streaming current measurements. We validate the performance of the setup by studying both bare SiN and polymer-coated nanopores fabricated by the controlled breakdown method. To address the issue of nanopore clogging, we investigate two distinct coating strategies, which involve functionalizing the surface either prior to or after pore formation, and thus targeting only the membrane outer surface, or also the pore interior, respectively. Selective coating is confirmed by characterizing the pores’ surface potential and conductance. Our results allow us to establish that membrane coating is sufficient to provide antifouling properties during biosensing of long single-stranded DNA. These findings highlight the importance of surface characterization and chemical modification in enhancing nanopore performance for single-molecule detection.