A counter-intuitive method for slowing down an analyte in a nanopore and its application to polymer sequencing and analysis

Abstract

AbstractA major obstacle in nanopore sensing for polymer sequencing, identification, and chemical analysis is the high translocation speed of an analyte (nucleotide, DNA, amino acid (AA), peptide) through the pore, about 10-100 monomers/μs, which exceeds the capability of currently available detectors. Attempts to resolve the problem fully have been less than satisfactory. Here a counter-intuitive method based on reversing the pore voltage and/or increasing analyte mobility by changing the solution pH is described. A simplified Fokker-Planck (F-P) model shows translocation times of 1-10 ms. More realistic simulations show that a bi-level positive-negative voltage profile can trap an analyte inside the pore for ~1 ms, which can be detected with a bandwidth of 1-10 Khz. This is a comprehensive approach to slowdown that can be used for free nucleotides, single amino acids, oligonucleotides/DNA strands, and oligopeptides/proteins. The applicability of this method to existing nanopore analysis techniques and issues relating to implementation are discussed.