Controlling DNA Tug-of-War in a Dual Nanopore Device

Methods for reducing and directly controlling the speed of DNA through a nanopore are needed to enhance sensing performance for direct strand sequencing and mapping of sequence-specific features. We have created a method for reducing and controlling the speed of DNA that uses two independently controllable nanopores operated with an active control logic. The pores are positioned sufficiently close to permit co-capture of a single DNA by both pores. Control logic then turns on constant competing voltages at the pores leading to a ''tug-of-war'' whereby the molecule is pulled from both ends by opposing forces. These forces exert both conformational and speed control over the co-captured molecule, removing folds and reducing the translocation rate. When the voltages are tuned so that the electrophoretic force applied to both ends of the molecule comes into balance, the life-time of the tug-of-war state is limited purely by diffusive sliding of the DNA between the pores (yielding a two order of magnitude enhancement in translocation time). We quantify the translocation slow-down as a function of voltage tuning and show that the slow-down is well described by a first passage analysis for a one-dimensional sub-diffusive process.