A Solid-state Sub-nm Pore for Single-mer Resolution Sequencing

Dehua Hu; Ho-Pui Ho; Jianxin Yang; Tianle Pan; Wu Yuan

arxiv: 2605.22381 · v1 · pith:2COCJPDTnew · submitted 2026-05-21 · ⚛️ physics.app-ph

A Solid-state Sub-nm Pore for Single-mer Resolution Sequencing

Jianxin Yang , Dehua Hu , Wu Yuan , Tianle Pan , Ho-Pui Ho This is my paper

Pith reviewed 2026-05-22 01:56 UTC · model grok-4.3

classification ⚛️ physics.app-ph

keywords nanopore sequencingsolid-state poresingle-mer resolutiondisplacement currentDNA sequencingpeptide sequencingelectric double layersub-nm resolution

0 comments

The pith

A sub-nanometer oxidized silicon pore detects individual DNA bases and amino acids directly via displacement currents with raw accuracies above 98.5 percent.

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The paper introduces a three-terminal platform built around an oxidized pyramidal sub-nm pore that serves as an electrode. This setup senses displacement currents generated by counter-ion motion inside the electric double layer at the pore surface. The approach yields sub-1-nm spatial resolution and signal-to-noise ratios up to 15, which the authors use to identify single bases in single-stranded DNA and single amino acids in peptides. Raw-read accuracies exceed 98.5 percent for DNA and 95.5 percent for peptides without any consensus correction or post-processing. The device also shows acid tolerance, reusability, and stability for more than six months, offering a durable alternative to synthesis-based sequencing methods.

Core claim

The authors demonstrate that an oxidized pyramidal sub-nm pore integrated in a three-terminal sensing platform functions as an electrode to detect displacement currents across an oxide barrier induced by counter-ion migration within the electric double layer. This configuration delivers sub-1-nm-scale spatial resolution and SNR values up to 15, enabling direct identification of individual bases in single-stranded DNA and single amino acids in peptides with raw-read accuracies exceeding 98.5 percent and 95.5 percent respectively, without consensus-based computational correction. The platform maintains high acid tolerance, reusability across chemical environments, and operational stability for

What carries the argument

The oxidized pyramidal sub-nm pore (OPSP) in a three-terminal platform that detects displacement currents from counter-ion migration in the electric double layer.

If this is right

Direct single-mer identification becomes possible without computational consensus or base-calling algorithms.
The same platform can sequence both DNA and peptides at high raw accuracy.
Long-term stability over six months and reusability reduce device replacement costs in sequencing workflows.
Acid tolerance expands the range of chemical conditions under which sequencing can occur.
Displacement-current sensing bypasses limitations of traditional current-blockade or synthesis-based methods.

Where Pith is reading between the lines

These are editorial extensions of the paper, not claims the author makes directly.

Arraying multiple OPSP sensors on a single chip could raise throughput while preserving single-mer resolution.
The electrical-double-layer mechanism might extend to sequencing other charged biopolymers or modified nucleotides not tested in the paper.
Integration with standard semiconductor fabrication lines could lower per-run costs compared with biological nanopore systems.
Portable or field-deployable sequencers become more feasible if the platform maintains performance at reduced voltages or buffer volumes.

Load-bearing premise

The sub-nm silicon pore reliably acts as an electrode that isolates and records displacement currents from counter-ion movement without interference from other ionic or electronic sources.

What would settle it

An experiment that measures translocation events through the pore while recording both the electrical signal and independent optical or mass-spectrometry identification of each base or amino acid, then shows that the claimed raw accuracies fall below 90 percent or that spatial resolution exceeds 1 nm.

Figures

Figures reproduced from arXiv: 2605.22381 by Dehua Hu, Ho-Pui Ho, Jianxin Yang, Tianle Pan, Wu Yuan.

**Figure 2.** Figure 2: Sequencing under non-equilibrium ionic concentrations across the pore. a, Schematic illustration of sequencing of ssDNA under a non-equilibrium ionic condition (1 M KCl in pore with deionized water outside) and an applied voltage U1 of 1.5V. The red arrow (Fep) and brown arrow (Feo) denote the electrophoretic and electroosmotic forces exerting on the ssDNA molecules, respectively, which Feo substantially s… view at source ↗

**Figure 4.** Figure 4: Sequencing the constituent peptides of insulin. a and b, Representative current trace (b) and distribution of current amplitude (ΔI) versus dwell time (Δt) (c) for 200 translocation events measured using the OPSP under the non-equilibrium ionic condition with U1 of 1.5V. The signal traces were obtained after a 100nM insulin sample had been incubated to dissociate the molecules into its constituent peptides… view at source ↗

read the original abstract

Nanopore sequencing accuracy is inherently limited by the quality of data from individual molecular translocation events, requiring advances beyond traditional sequencing-by-synthesis methods. We introduce an oxidized pyramidal sub-nm pore (OPSP) integrated in a threeterminal sensing platform, where the sub-nm silicon pore functions as an electrode for detecting displacement currents across an oxide barrier, induced by counter-ion migration within the electric double layer. This platform achieves sub-1-nm-scale spatial resolution and a signal-tonoise ratio (SNR) up to 15 for biopolymer sequencing, enabling direct identification of individual bases in single-stranded DNA and single amino acids in peptides, with raw-read accuracies exceeding 98.5% and 95.5%, respectively, without consensus-based computational correction. The OPSP demonstrates high acid tolerance, reusability in varied chemical environments, and operational stability for over six months. This work establishes OPSP as a durable, high-accuracy platform for single-mer resolution sequencing, defining a reliable and robust paradigm for next-generation sequencing technologies.

Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, simulated authors' rebuttal, and a circularity audit. Tearing a paper down is the easy half of reading it; the pith above is the substance, this is the friction.

Desk Editor's Note private letter to a colleague

OPSP offers a durable solid-state option for high-accuracy single-mer sequencing but the displacement current claims need stronger experimental controls to be convincing.

read the letter

The key takeaway is that this work describes an oxidized pyramidal sub-nm pore in a three-terminal platform that uses displacement current sensing to achieve direct single-mer identification in DNA and peptides, with reported raw accuracies over 98% and 95% without computational help. What is new is the specific OPSP design where the sub-nm silicon pore acts as an electrode detecting currents across an oxide barrier from counter-ion migration in the electric double layer. The paper does well in emphasizing the practical aspects, such as high acid tolerance, reusability, and stability for more than six months, which addresses common durability issues in solid-state nanopores. The approach moves beyond sequencing-by-synthesis by aiming for direct base and amino acid detection with sub-1-nm resolution and SNR up to 15. If the data supports it, this could simplify workflows in genomics and proteomics. The soft spots center on confirming the signal is truly from the intended mechanism. The stress-test concern about lacking controls for ionic or capacitive interference is worth checking in the full text. Without frequency-dependent data or specific control experiments like zero-bias or blocked pore conditions, it's possible other effects contribute to the signal. The accuracies are stated clearly but the abstract and any methods summary would benefit from more on how the signals were assigned to specific mers and any variability observed. Even with the full manuscript, more raw data traces and details on the identification process would help. This paper is for specialists in nanopore sequencing and nanoscale sensors. A reader working on solid-state devices for biopolymer analysis would get value from the platform description and claimed performance. I would recommend sending it for peer review. The idea is worth serious evaluation even if revisions are needed to strengthen the experimental validation.

Referee Report

2 major / 1 minor

Summary. The paper introduces an oxidized pyramidal sub-nm pore (OPSP) integrated in a three-terminal sensing platform, where the sub-nm silicon pore functions as an electrode detecting displacement currents across an oxide barrier induced by counter-ion migration in the electric double layer. It claims sub-1-nm spatial resolution, SNR up to 15, direct single-mer identification of DNA bases and peptide amino acids with raw accuracies >98.5% and >95.5% respectively without computational correction, plus high durability, acid tolerance, reusability, and stability over six months.

Significance. If the results and mechanistic claims hold with adequate verification, this would represent a notable advance in solid-state nanopore sequencing by enabling high raw accuracy and SNR for single-mer resolution without post-processing, potentially simplifying workflows and offering a robust, reusable platform for next-generation sequencing.

major comments (2)

[Abstract] Abstract: The claims of raw-read accuracies exceeding 98.5% (DNA) and 95.5% (peptides), sub-1-nm resolution, and SNR up to 15 are stated without any accompanying data, error bars, sample sizes, statistical methods, or verification steps, preventing evaluation of these performance metrics against the manuscript's evidence.
[Sensing mechanism] Sensing mechanism (abstract and platform description): The central interpretation that the oxidized pore detects only displacement currents from EDL counter-ion migration, enabling direct identification without interference, lacks supporting controls such as frequency-dependent measurements, blocked-pore tests, zero-bias conditions, or equivalent-circuit analysis to exclude ionic conduction through the pore, oxide pinholes, or standard capacitive coupling.

minor comments (1)

[Abstract] Abstract: The acronym 'OPSP' is introduced but its full expansion and relation to the three-terminal platform could be clarified earlier for readability.

Simulated Author's Rebuttal

2 responses · 0 unresolved

We thank the referee for their constructive comments and the opportunity to clarify the presentation of our results on the oxidized pyramidal sub-nm pore platform. We respond to each major comment below.

read point-by-point responses

Referee: [Abstract] Abstract: The claims of raw-read accuracies exceeding 98.5% (DNA) and 95.5% (peptides), sub-1-nm resolution, and SNR up to 15 are stated without any accompanying data, error bars, sample sizes, statistical methods, or verification steps, preventing evaluation of these performance metrics against the manuscript's evidence.

Authors: We agree that the abstract, by design, presents the performance claims concisely without the full statistical details. The manuscript body reports the supporting evidence through raw current traces, amplitude histograms, and direct sequence-matching calculations for accuracy, with the relevant sample sizes, error representations, and verification approach described in the Results and Methods sections. To address the concern, we will revise the abstract to include a short clause referencing the figures and sections that contain the underlying data and statistical methods. revision: yes
Referee: [Sensing mechanism] Sensing mechanism (abstract and platform description): The central interpretation that the oxidized pore detects only displacement currents from EDL counter-ion migration, enabling direct identification without interference, lacks supporting controls such as frequency-dependent measurements, blocked-pore tests, zero-bias conditions, or equivalent-circuit analysis to exclude ionic conduction through the pore, oxide pinholes, or standard capacitive coupling.

Authors: The three-terminal geometry and sub-nm oxide barrier are central to our interpretation, and the observed spatial resolution and SNR values are difficult to reconcile with bulk ionic conduction or simple capacitive coupling. We acknowledge that explicit controls would strengthen the mechanistic claim. In revision we will add an equivalent-circuit analysis section and expanded discussion of why alternative pathways are inconsistent with the data; we will also highlight any existing experimental conditions that already constrain those alternatives. revision: partial

Circularity Check

0 steps flagged

No derivation chain present; claims are direct experimental reports

full rationale

The manuscript reports fabrication and testing of an oxidized pyramidal sub-nm pore in a three-terminal platform, with performance metrics (sub-1-nm resolution, SNR up to 15, raw accuracies >98.5% DNA and >95.5% peptides) presented as measured outcomes of the physical device. No equations, parameter fits, model predictions, or self-cited uniqueness theorems appear in the provided text. The central claims rest on experimental observation rather than any reduction to prior inputs or fitted quantities, satisfying the self-contained criterion.

Axiom & Free-Parameter Ledger

0 free parameters · 0 axioms · 0 invented entities

The abstract describes an experimental device and its performance without any mathematical derivations, fitted parameters, or theoretical axioms. The OPSP is introduced as a fabricated structure rather than a postulated theoretical entity.

pith-pipeline@v0.9.0 · 5715 in / 1130 out tokens · 69805 ms · 2026-05-22T01:56:06.661352+00:00 · methodology

discussion (0)

Lean theorems connected to this paper

Citations machine-checked in the Pith Canon. Every link opens the source theorem in the public Lean library.

IndisputableMonolith/Foundation/AbsoluteFloorClosure.lean reality_from_one_distinction unclear

?

unclear
Relation between the paper passage and the cited Recognition theorem.

oxidized pyramidal sub-nm pore (OPSP) integrated in a three-terminal sensing platform, where the sub-nm silicon pore functions as an electrode for detecting displacement currents across an oxide barrier, induced by counter-ion migration within the electric double layer

What do these tags mean?

matches: The paper's claim is directly supported by a theorem in the formal canon.
supports: The theorem supports part of the paper's argument, but the paper may add assumptions or extra steps.
extends: The paper goes beyond the formal theorem; the theorem is a base layer rather than the whole result.
uses: The paper appears to rely on the theorem as machinery.
contradicts: The paper's claim conflicts with a theorem or certificate in the canon.
unclear: Pith found a possible connection, but the passage is too broad, indirect, or ambiguous to say the theorem truly supports the claim.

Reference graph

Works this paper leans on

1 extracted references · 1 canonical work pages

[1]

|0#$!%&$

A Solid-state Sub-nm Pore for Single-mer Resolution Sequencing Jianxin Yang†, Dehua Hu†, Wu Yuan†, Tianle Pan, and Ho-Pui Ho* Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China. *Corresponding author. Email: aaron.ho@cuhk.edu.hk (H.-P.H.). †The three authors contributed equally to this work. Abstract Nanopore s...

work page 2016

[1] [1]

|0#$!%&$

A Solid-state Sub-nm Pore for Single-mer Resolution Sequencing Jianxin Yang†, Dehua Hu†, Wu Yuan†, Tianle Pan, and Ho-Pui Ho* Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China. *Corresponding author. Email: aaron.ho@cuhk.edu.hk (H.-P.H.). †The three authors contributed equally to this work. Abstract Nanopore s...

work page 2016