Controlling Electroosmosis in Nanopores Without Altering the Nanopore Sensing Region

Nanopores are powerful tools for single-molecule sensing of biomolecules and nanoparticles. The signal coming from the molecule to be analyzed strongly depends on its interaction with the narrower section of the nanopore (constriction) that may be tailored to increase sensing accuracy. Modifications of nanopore constriction have also been commonly used to induce electroosmosis, that favors the capture of molecules in the nanopore under a voltage bias and independently of their charge. However, engineering nanopores for increasing both electroosmosis and sensing accuracy is challenging. Here it is shown that large electroosmotic flows can be achieved without altering the nanopore constriction. Using continuum electrohydrodynamic simulations, it is found that an external charged ring generates strong electroosmosis in cylindrical nanopores. Similarly, for conical nanopores it is shown that moving charges away from the cone tip still results in an electroosmotic flow (EOF), whose intensity reduces increasing the diameter of the nanopore section where charges are placed. This paradigm is applied to engineered biological nanopores showing, via atomistic simulations and experiments, that mutations outside the constriction induce a relatively intense electroosmosis. This strategy provides much more flexibility in nanopore design since electroosmosis can be controlled independently from the constriction, which can be optimized to improve sensing accuracy.