Translocation of Specific DNA Nanocarrier through an Ultrasmall Nanopipette: Toward Single-Protein-Molecule Detection with Superior Signal-to-Noise Ratio

The use of functional DNA nanostructures as carriers to ship proteins through solid-state nanopores has recently seen substantial growth in single-protein-molecule detection (SPMD), driven by the potential of this methodology and implementations that it may enable. Ultrasmall nanopores have exhibite...

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Bibliographic Details
Published inACS nano Vol. 16; no. 9; pp. 15108 - 15114
Main Authors Zhang, Xian, Luo, Dan, Zheng, You-Wei, Li, Xiao-Qiong, Song, Juan, Zhao, Wei-Wei, Chen, Hong-Yuan, Xu, Jing-Juan
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 27.09.2022
Subjects
Acetylcholinesterase
Aptamers, Nucleotide
Dimaprit - analogs & derivatives
DNA - chemistry
Humans
Nanopores
Signal-To-Noise Ratio
DNA nanostructure
ultrasmall nanopipette
resistive pulse sensing
single-protein detection
signal-to-noise ratio
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Summary:The use of functional DNA nanostructures as carriers to ship proteins through solid-state nanopores has recently seen substantial growth in single-protein-molecule detection (SPMD), driven by the potential of this methodology and implementations that it may enable. Ultrasmall nanopores have exhibited obvious advantages in spatiotemporal biological detection due to the appropriate nanoconfined spaces and unique properties. Herein, a 6.8 nm DNA tetrahedron (TDN) with a target-specific DNA aptamer (TDN-apt) was engineered to carry the representative target of acetylcholinesterase (AChE) through an ultrasmall nanopipet with a 30 nm orifice, underpinning the advanced SPMD of AChE with good performance in terms of high selectivity, low detection limit (0.1 fM), and especially superior signal-to-noise ratio (SNR). The kinetic interaction between TDN-apt and AChE was studied and the practical applicability of the as-developed SPMD toward real samples was validated using serum samples from patients with Alzheimer’s disease. This work not only presented a feasible SPMD solution toward low-abundance proteins in complex samples and but also was envisioned to inspire more interest in the design and implementation of synergized DNA nanostructure–ultrasmall nanopore systems for future SPMD development.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.2c06303