Enhanced detection of low-surface-charge nanoparticles via pressure regulation in solid-state nanopores

Nanopore detection technology is a high-sensitivity analysis method with essential applications in DNA sequencing, protein identification, and other fields. However, conventional electrophoretic driving has limited efficiency in detecting nanoparticles with low surface charge. In this work, a strategy combining pressure-driven and electrophoretic forces was proposed to improve the detection performance of complex nanoparticle systems in solid-state nanopores. By optimizing the pressure and electric-field parameters, the translocation frequency of a single nanoparticle type with low surface charge was increased, and mixed particles of different sizes and charges were discriminated. Notably, we observed a new phenomenon in which particle translocation frequency increased only under the electrophoretic force after mixing oppositely charged nanoparticles without requiring external pressure. This study demonstrated that synergistic pressure and electric-field driving can provide a more flexible and efficient approach towards single-molecule detection, thereby expanding nanopore applications for biological nanoparticle and small-molecule analysis.