Precise Positional Readout of Molecular Barcode Structures using Solid-State Nanopores
Abstract
Fast and nonuniform translocation through solid-state nanopores limits both the detection of small molecular labels and their precise localization along molecular carriers. In this work we report the detection and localization performance of nucleotide-based molecular labels along double-stranded DNA scaffolds using solid-state nanopores in thin planar membranes. For small labels that are challenging to resolve individually, we introduce an anchoring strategy where readily detectable bulky labels serve as reference points to align multiple translocation events, enabling population-based detection and localization of smaller molecular features. The measured anchor positions constrain a probabilistic model of translocation velocity, identifying the most probable velocity profile for each event and enabling nonlinear trace "unwarping" for improved multi-event alignment. A complementary window-based evidence aggregation procedure accumulates weak but consistent label signatures across events, enabling detection of features that are individually masked by noise. These approaches enable robust recovery of single-dumbbell labels (DB1) on the order of 28 nucleotides and reduce mean localization errors to as low as 10 base pairs for DB3 labels and 40 base pairs for DB1 labels when averaging over multiple events. Stronger fractional DNA-associated current blockades, used as proxy for smaller pore geometries, are additionally associated with improved detection and lower localization error across membrane-based nanopore fabrication techniques. Overall, anchor-guided alignment provides a route to higher-density molecular information readout without compromising throughput via controlled translocation approaches.
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BibTeX
@misc{botermans2026precise,
title = {{Precise Positional Readout of Molecular Barcode Structures using Solid-State Nanopores}},
author = {Wouter Botermans and Eric Beamish and Matteo Cartiglia and Liam Vandekerckhove and Wouter Renckens and Natan Biesmans and Koen Ongena and Wannes Peeters and Pol Van Dorpe and Sanjin Marion},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2609.05445},
eprint = {2609.05445},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2609.05445},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Precise Positional Readout of Molecular Barcode Structures using Solid-State Nanopores
AU - Wouter Botermans
AU - Eric Beamish
AU - Matteo Cartiglia
AU - Liam Vandekerckhove
AU - Wouter Renckens
AU - Natan Biesmans
AU - Koen Ongena
AU - Wannes Peeters
AU - Pol Van Dorpe
AU - Sanjin Marion
PY - 2026
DA - 2026/09/01
PB - arXiv
DO - 10.48550/arxiv.2609.05445
UR - https://arxiv.org/abs/2609.05445
AB - Fast and nonuniform translocation through solid-state nanopores limits both the detection of small molecular labels and their precise localization along molecular carriers. In this work we report the detection and localization performance of nucleotide-based molecular labels along double-stranded DNA scaffolds using solid-state nanopores in thin planar membranes. For small labels that are challenging to resolve individually, we introduce an anchoring strategy where readily detectable bulky labels serve as reference points to align multiple translocation events, enabling population-based detection and localization of smaller molecular features. The measured anchor positions constrain a probabilistic model of translocation velocity, identifying the most probable velocity profile for each event and enabling nonlinear trace "unwarping" for improved multi-event alignment. A complementary window-based evidence aggregation procedure accumulates weak but consistent label signatures across events, enabling detection of features that are individually masked by noise. These approaches enable robust recovery of single-dumbbell labels (DB1) on the order of 28 nucleotides and reduce mean localization errors to as low as 10 base pairs for DB3 labels and 40 base pairs for DB1 labels when averaging over multiple events. Stronger fractional DNA-associated current blockades, used as proxy for smaller pore geometries, are additionally associated with improved detection and lower localization error across membrane-based nanopore fabrication techniques. Overall, anchor-guided alignment provides a route to higher-density molecular information readout without compromising throughput via controlled translocation approaches.
ER -