Self-referenced readout of nanopore translocation signals using localized electrometry

For the past two decades, the ionic current blockade-based readout approach has been the basis of nanopore single-molecule sensing technology. Here, we introduce "nanopore electrometry," a readout method based on measuring the modulation of the local electric field due to the translocation of the target molecule. Through comprehensive multiphysics and molecular dynamics simulations, we establish the unique strengths of nanopore electrometry that can open up new frontiers in nanopore based molecular detection. For instance, electric field concentration inside the nanopore combined with the rapid decay of the field due to charge screening leads to an asymmetric sensitivity of nanopore electrometry to the charge of the target, i.e., one can sense only cations or only anions depending on the location of the electric field sensor or the direction of the external electric field. Furthermore, simultaneous measurements from multiple local electric field sensors can be utilized for self-referenced error correction and to compensate for translocation velocity fluctuations. Finally, nanopore electrometry can also be used to detect translocations without requiring liquid electrolytes.