Working Paper Short Note Version 1 This version is not peer-reviewed

A Counterintuitive Method for Slowing Down an Analyte in a Nanopore by Reversing the Pore Voltage and Increasing Analyte Mobility

Version 1 : Received: 13 January 2021 / Approved: 14 January 2021 / Online: 14 January 2021 (09:53:00 CET)

How to cite: Sampath, G. A Counterintuitive Method for Slowing Down an Analyte in a Nanopore by Reversing the Pore Voltage and Increasing Analyte Mobility. Preprints 2021, 2021010265 Sampath, G. A Counterintuitive Method for Slowing Down an Analyte in a Nanopore by Reversing the Pore Voltage and Increasing Analyte Mobility. Preprints 2021, 2021010265

Abstract

A major obstacle faced by nanopore-based polymer sequencing and analysis is the high speed of translocation of an analyte (nucleotide, DNA, amino acid (AA), peptide) through the pore; the rate currently exceeds available detector bandwidth. Except for one method that uses an enzyme ratchet to sequence DNA, attempts to resolve the problem satisfactorily have been largely unsuccessful. Here a counterintuitive method based on reversing the pore voltage, and, with some analytes, increasing their mobility, is described. A simplified Fokker-Planck model shows a significant increase in translocation times for single nucleotides and AAs (up from ~10 ns to ~1 ms). More realistic simulations show that with a bi-level positive-negative pore voltage profile all four nucleotides in DNA (dAMP, dTMP, dCMP, and dGMP) and the 20 proteinogenic amino acids can be trapped inside the pore long enough for detection with bandwidths of ~1-10 Khz.

Subject Areas

nanopore; translocation slowdown; mobility; polymer sequencing; bandwidth; diffusion

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