Deterministic control of polymer molecule translocation through a nanopore

A method for determining a sequence of nucleotides of a target polymer molecule having a target polymer molecule length comprising a plurality of nucleotides, comprising:

• reversibly binding a clamp to the target polymer molecule at a site along the target polymer molecule length;
• after binding the clamp to the target polymer molecule, disposing the target polymer molecule and the reversibly-bound clamp in an ionic solution that is in fluidic communication with a nanopore, the nanopore having an aperture diameter less than an outer diameter of the clamp;
• applying a constant translocation force across the nanopore to induce travel of the target polymer molecule in the ionic solution into the nanopore such that the reversibly bound clamp abuts the nanopore;
• applying across the nanopore a voltage pulse that advances the target polymer molecule into the nanopore by one nucleotide, without providing either of chemical fuel and biochemical fuel to the clamp;
• acquiring a representative indication of a nucleotide as the nucleotide translocates through the nanopore;
• and
• repeatedly applying the voltage pulse to cause a plurality of nucleotides to translocate through the nanopore, with a repetition of voltage pulse application after each acquisition of a representative indication of a nucleotide.

A method for determining a sequence of nucleotides of a target polymer molecule having a target polymer molecule length comprising a plurality of nucleotides, comprising:

• disposing the target polymer molecule and a clamp in an ionic solution that is in fluidic communication with a nanopore, the nanopore having an aperture diameter less than an outer diameter of the clamp;
• after disposing the target polymer molecule and the clamp in an ionic solution, reversibly binding the clamp to the target polymer molecule in the ionic solution at a site along the target polymer molecule length;
• applying a constant translocation force across the nanopore to induce travel of the target polymer molecule in the ionic solution into the nanopore such that the reversibly bound clamp abuts the nanopore;
• applying across the nanopore a voltage pulse that advances the target polymer molecule into the nanopore by one nucleotide, without providing either of chemical fuel and biochemical fuel to the clamp;
• acquiring a representative indication of a nucleotide as the nucleotide translocates through the nanopore;
• and
• repeatedly applying the voltage pulse to cause a plurality of nucleotides to translocate through the nanopore, with one repetition of voltage pulse application after each acquisition of a representative indication of a nucleotide.