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Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores
Published on: October 31, 2013
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Flossing DNA in a Dual Nanopore Device
Xu Liu1, Philip Zimny1, Yuning Zhang2
1Ontera Inc., Santa Cruz, CA, 95060, USA.
Small (Weinheim an Der Bergstrasse, Germany)
|December 21, 2019
Summary
Active control using dual solid-state nanopores, termed "flossing," significantly reduces molecular noise in single-molecule DNA mapping. This technique improves DNA linearization and enables precise mapping of molecular motifs for genomic applications.
Area of Science:
- Biophysics
- Nanotechnology
- Genomics
Background:
- Solid-state nanopores offer single-molecule analysis, overcoming ensemble averaging limitations.
- Mapping molecular motifs on DNA using nanopores and barcoding is promising but hindered by noise.
- Existing methods struggle with molecular noise and DNA linearization for accurate mapping.
Purpose of the Study:
- To introduce an active control technique called "flossing" using a dual nanopore device.
- To suppress molecular noise and enhance DNA linearization for precise single-molecule mapping.
- To demonstrate the utility of flossing for genome mapping and structural variation analysis.
Main Methods:
- Utilized a dual nanopore device for active control and trapping of protein-tagged DNA molecules.
- Performed hundreds of bidirectional electrical scans of DNA molecules within seconds.
- Employed protein motifs on λ-DNA as detectable features for triggering bidirectional control.
Main Results:
- Flossing suppressed molecular noise by averaging multiscan data, yielding accurate inter-tag distance estimates.
- Achieved >98% trans-pore DNA linearization by the second scan, a significant improvement over single-pore passage (35%).
- Demonstrated comparable inter-tag distance estimates to known values for protein motifs on λ-DNA.
Conclusions:
- The dual-pore flossing technique effectively reduces noise and enhances DNA linearization for single-molecule mapping.
- This method shows potential for applications in genome mapping, structural variation analysis, and epigenetic locus mapping.
- Flossing, combined with barcoding, advances the capabilities of nanopore-based molecular analysis.
