DNA Flossing in a Dual Pore Device

Solid-state nanopores are a leading technology for label-free single-molecule sensing of DNA. However, fundamental challenges hinder exploitation of solid-state pore devices: the need to (1) ensure molecule linearization (eliminate folding), (2) reduce effect of molecular fluctuations that introduce random error and (3) perform accurate genomic distance calibration. Two-pore devices with active control have potential to address these challenges. We have developed a feedback-driven dynamic control approach based on Field Programmable Gate Arrays that can adjust the opposing forces during translocation so as to scan the DNA molecule back and forth (“DNA flossing” [1-3]) This multi-scanning capability reduces random error by enabling averaging over repeated scans of linearized molecules. We demonstrate ability to perform 100’s of multi-scan cycles of a DNA molecule labeled with sequence specific tags and present simulation motivated analysis protocols for performing optimal time to sequence domain calibration of extracted barcodes.
[1] Y. Zhang et al, Small, 2018; [2] X. Liu et al, Small, 2019; [3]; X. Liu et al, Small, 2020