Accurate discrimination of amyloid-β (Aβ) peptides containing familial point mutations would advance the knowledge of their roles in early-onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild-type (WT) Aβ 18-26 peptides with aerolysin nanopore using a 3D blockage mapping strategy. The standard deviation of current blockade fluctuations (σ b ) was proposed as a new supplement to current blockage (I b /I 0 ) and duration time (t D ) to profile the blockage characteristics of single molecules. Although the WT and A21G Aβ 18-26 are indistinguishable in a traditional I b /I 0 -t D 2D description, ~87 % of the blockade events can be accurately classified with half reduction of false identification using a combination of I b /I 0 , t D, and σ b . This work offers an easy and reliable strategy to promote nanopore sensitivity of peptide mutants, leading to a more precise analysis of pathogenic mutations for developing effective diagnosis and treatment.

Accurate discrimination of amyloid-β (Aβ) peptides containing familial point mutations would advance the knowledge of their roles in early-onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild-type (WT) Aβ 18-26 peptides with aerolysin nanopore using a 3D blockage mapping strategy. The standard deviation of current blockade fluctuations (σ b ) was proposed as a new supplement to current blockage (I b /I 0 ) and duration time (t D ) to profile the blockage characteristics of single molecules. Although the WT and A21G Aβ 18-26 are indistinguishable in a traditional I b /I 0 -t D 2D description, ~87 % of the blockade events can be accurately classified with half reduction of false identification using a combination of I b /I 0 , t D, and σ b . This work offers an easy and reliable strategy to promote nanopore sensitivity of peptide mutants, leading to a more precise analysis of pathogenic mutations for developing effective diagnosis and treatment.

Sequence-defined polymer is one of the most promising alternative media for high-density data storage. It could be used to alleviate the problem of insufficient storage capacity of conventional silicon-based devices for the explosively increasing data. To fulfil the goal of polymer data storage, suitable methods should be developed to accurately read and decode the information-containing polymers, especially for those composed by a combination of the natural and unnatural monomers. Nanopore-based ap-proaches have become one of the most competitive analysis and sequencing techniques, which are expected to read both natural and synthetic polymers with single-molecule precision and monomeric resolution. Herein, this work emphasizes the advances being made in nanopore reading and decoding of information stored in the man-made polymers and DNA nanostructures, and discusses the challenges and opportunities towards the development and realization of high-density data storage.

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