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Related Concept Videos

NMR Spectrometers: Resolution and Error Correction01:14

NMR Spectrometers: Resolution and Error Correction

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When magnetic nuclei in a sample achieve resonance and undergo relaxation, the signal detected in NMR is an approximately exponential free induction decay. Fourier transform of an exponential decay yields a Lorentzian peak in the frequency domain. Lorentzian peaks in an NMR spectrum are defined by their amplitude, full width at half maximum, and position, where the peak width is governed by the spin-spin relaxation time alone. In real experiments, however, the applied magnetic field is rendered...
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Updated: Mar 27, 2026

Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores
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Zero-Dalton Resolution in Nanopore Peptide Recognition.

Mazdak Afshar Bakshloo1, Leïla Bechtella1, Jianjun Tao1

  • 1Université Paris-Saclay, Université Evry, CY Cergy Paris Université, CNRS, LAMBE, 91025 Evry-Courcouronnes, France.

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|March 25, 2026
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Summary
This summary is machine-generated.

Nanopore sensing can now distinguish between identical-mass peptides, even at full pore occupancy. This breakthrough in zero-dalton resolution relies on ion-specific effects and intrinsic structural differences, advancing molecular analysis.

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Area of Science:

  • Biophysics
  • Analytical Chemistry
  • Proteomics

Background:

  • Achieving zero-dalton resolution (discriminating molecules of identical mass) is a key challenge in molecular analysis.
  • Nanopore sensing has shown promise for resolving short peptide isomers, but its efficacy with longer peptides near nanopore saturation limits is uncertain.

Purpose of the Study:

  • To investigate the capability of nanopore sensing for discriminating between 13-residue α-synuclein isomers at near-full nanopore occupancy.
  • To explore the influence of ion type and concentration on peptide conformation and nanopore discrimination.

Main Methods:

  • Utilized wild-type aerolysin nanopores for sensing peptide isomers.
  • Employed ion mobility-mass spectrometry and molecular simulations for corroboration.
  • Investigated the effects of various salts (KCl, NaCl, LiCl, CaCl2) on peptide conformation and discrimination.

Main Results:

  • Demonstrated robust discrimination of 13-residue α-synuclein isomers using aerolysin nanopores at lengths approaching full occupancy.
  • Identified ion-specific effects: KCl and NaCl favored extended states, while LiCl and CaCl2 promoted compact, folded states that amplified discrimination, achieving up to 100% separation.
  • Showed that discrimination is robust and independent of peptide entry order, conformation, or translocation status.

Conclusions:

  • Full peptide accommodation within the nanopore, amplified by ion-specific conformational changes, enables zero-dalton resolution for longer isomers.
  • Exploiting folded or partially folded peptide states in nanopores offers a strategy for extending isomer discrimination to longer peptides.
  • This work provides a foundation for advancing single-molecule proteomics and molecular fingerprinting for complex biomolecules.