Recent research has showcased the potential of nanopores to detect molecular features along a DNA carrier strand, including proteins such as anti-DNA antibodies [5] and streptavidin, [6,7] singlestranded versus double-stranded regions of a molecule, [8] DNA-hairpins, [9,10] and aptamers. [11,12] Potential applications range from digital information storage, [9,10] multi plexed sensing, [9,11] and genomic and/or functional genomic applications including genome mapping [13] and epigenetics. [14,15] Solid-state pores in particular can target a more diverse analyte pool than protein pores [16] (e.g., dsDNA, proteins, nucleosomes [17] ) and thereby give access to a broad range of single-molecule applications.A key challenge in performing multilocus sensing of motifs along DNA is the inherent sensitivity of single-molecule systems to noise. Unwanted conformations/ topologies and molecular fluctuations (both equilibrium and nonequilibrium in nature) create systematic and random distortions in the electrical signal pattern of motifs resolved by the sensor. For example, closely spaced features along DNA cannot always be resolved in a given single-molecule read even with state-of-the-art measurements performed with 5 nm diameter nanopores, [10] requiring multiple independent reads from identical copies of different molecules to confidently resolve the features. In addition, the stochastic nature of the translocation process gives rise to broad distributions [18,19] in tag spacings measured across a molecular ensemble; [7] these broad distributions necessitate averaging over additional molecules to obtain precise spacing estimates. A related challenge is providing independent genomic distance calibration along individual single-molecule reads, so that sensor output can be linked to sequence position without a priori knowledge of the distance between motifs. While optics can provide high-resolution spatiotemporal data, [20,21] nanopores can only infer spatial information implicitly from temporal data. In order for nanopore technology to achieve its full potential, it is essential that singlemolecule reads have sufficient quality (e.g., contain sufficiently low systematic and random errors), so that the requirement for further ensemble-level averaging over different molecules is minimized or eliminated. The technology can then be applied to the complex, heterogeneous samples reflective of applications where every molecule may have a different number of bound motifs possessing a distinct spatial distribution.Solid-state nanopores are a single-molecule technique that can provide access to biomolecular information that is otherwise masked by ensemble averaging. A promising application uses pores and barcoding chemistries to map molecular motifs along single DNA molecules. Despite recent research breakthroughs, however, it remains challenging to overcome molecular noise to fully exploit single-molecule data. Here, an active control technique termed "flossing" that uses a dual nanopore device is presented to trap a proteintagged...