The Effects of Tetramethylammonium Cation on Oligonucleotide Analysis with Aerolysin Nanopore

Nanopore biosensors, as an extremely sensitive tool, are widely applied to single‐molecule analysis. Compared with the commonly used α‐hemolysin, aerolysin nanopore possess a narrower channel, which distributes the abundant charged residues in the lumen. We replaced the commonly used potassium cations (K + ) with tetramethylammonium cations (TMA + ) to explore the cation effects. Experimental results demonstrate that the blockage of oligonucleotides in the TMA + system is distinctly more considerable than that in K + system. In particular, the blockade currents of Poly(dA) 5 are very closed to 0 pA. In addition, the capture rate of oligonucleotides is distinctly increased, and it is speculated that amphipathic TMA + can enhance the affinity of aerolysin nanopore for oligonucleotides. Furthermore, the estimated effective charges ( Z inside ) of oligonucleotides inside aerolysin nanopore in two solutions suggest that the screening of K + on Poly(dA) 3 , Poly(dA) 4 , and Poly(dA) 5 is more effective than that for TMA + . This report deepens our understanding of the effects of cations in electrolyte.