Preparation of a novel solid-state sub-nanopore and its application in protein sequencing

CN116969411BActive Publication Date: 2026-06-30CENT SOUTH UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-04-25
Publication Date
2026-06-30

AI Technical Summary

Technical Problem

Existing biological nanopores are difficult to use effectively for protein sequencing due to their large pore size and insufficient sensing region depth, resulting in low signal-to-noise ratios and making it difficult to replicate their success in gene sequencing.

Method used

Solid-state sub-nanopores with pore sizes of 0.3-0.7 nm were prepared on pure silicon thin films using scanning transmission electron microscopy. Their spatial structure and electric field distribution were verified by multilayer image simulation and finite element simulation. Protein single-molecule sequencing was performed by combining machine learning algorithms.

Benefits of technology

It achieves efficient sequencing of single protein molecules with a sensing region depth of less than 1 nm, enabling specific detection of single residues and improving the throughput and accuracy of sequencing data acquisition.

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Abstract

This invention belongs to the field of protein sequencing, specifically disclosing a novel solid-state sub-nanopore fabrication method and its application in protein sequencing. The technical solution involves: reliably and easily fabricating pores with a diameter less than 1 nm on a 5 nm thick pure silicon film; reconstructing the spatial structure of the pores in three dimensions at the atomic scale through transmission electron microscopy imaging and multilayer image simulation comparison; and then incorporating key geometric parameters into finite element multiphysics modeling to simulate the electric field distribution within the pores and calculate the conductivity of the sub-nanopores, thereby evaluating the application potential and performance of this fabrication method in protein single-molecule sequencing. The sensing region depth of this novel nanopore can be less than 1 nm, giving it an advantage over other similar nanopores in developing protein de novo sequencing technology with single-point residue specificity (kmer=1), providing a new approach for the single-point residue specificity detection of protein variants.
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Citation Information

Patent Citations

  • Nanopore arrays and sequencing devices and methods thereof

    US20080254995A1